Challenging Case: A Multidisciplinary Approach to Demystifying Chronic Sleep Impairment in an Infant with a Complex Medical and Behavioral Profile.

CASE: X is a 22-month-old White male infant with a complex medical history, including diagnoses of FBXO11 mutation, hypotonia, restrictive lung disease and mild intermittent asthma, laryngotracheomalacia, obstructive sleep apnea (OSA), feeding difficulties with a history of aspiration, gastroesophageal reflux disease (GERD), and developmental delays. X's medical presentation has resulted in multiple prior medical admissions for respiratory failure due to acute illnesses, procedures and treatments including gastrojejunostomy (GJ) tube dependence, supraglottoplasty to reshape tissues of the upper larynx, and the use of biphasic positive airway pressure (BiPAP) at night and room air during the day when he is at baseline. In addition, he has nocturnal events characterized by significant agitation, screaming, crying, body stiffening and limb movements with pauses in breathing, mouth breathing, restless sleep, and difficulty waking in the morning with concomitant daytime fatigue despite above treatments for OSA. There is no history of congenital heart disease or sudden unexplained death. Family history is noncontributory because parents are negative for the FBXO11 variant.X's sleep disruption has led to significant sleep deficits for both X and his caregivers, who spend much of the night strategizing on how to console him. X has undergone several sleep studies, starting when X was aged 4 months, at several children's hospitals across the nation to determine the cause of his chronic sleep disturbance, which yielded limited information and treatment success. As an infant, X received a medical workup and was subsequently treated with a proton pump inhibitor (PPI) for reflux. At 12 months, he was diagnosed with disordered sleep with myoclonic jerks and started on melatonin and gabapentin for involuntary movements. At 13 months, gabapentin was weaned back because of intolerance, and at 15 months, nortriptyline and clonidine were started because of worsening symptoms to target potential neuropathic pain. While most of his symptoms were at night, he had occasional daytime screaming episodes, particularly when experiencing illness. Gabapentin and clonidine were stopped because nortriptyline seemed most effective.At 17 months, the results from a sleep study led to a diagnosis of night terrors, and several clinicians agreed that X's sleep disruption was behavioral in nature. At this time, an infant mental health consultant met with a sleep psychologist on the family's behalf to support family in considering systematic desensitization therapy to increase tolerance to wearing his BiPAP mask, as well as other behavioral and sleep hygiene strategies, which were tried on several occasions and again, resulted in limited improvement in functioning.At 19 months, X's multidisciplinary team reconsidered a night terror diagnosis after a failed trial of clonazepam and pursued a differential diagnosis of periodic limb movement disorder (PLMD). X trialed gabapentin again, but this time only a nighttime dose, per sleep medicine and psychiatry recommendation. While this brought some temporary relief from nighttime distress, despite increasing to the highest dose for age and weight (15 mg/kg/dose), this became less effective, and he was weaned off at 22 months. He had been on iron supplementation since age 6 months and received an iron infusion at 22 months because of persistently low ferritin levels and PLMD in sleep.At 24 months, X was briefly trialed on levetiracetam. While no evidence for seizures on EEG was present, this medication was chosen for involuntary movements and genetic risk for seizures. However, this medication was not useful. At 25 months, an evaluation with a movement disorder physiatrist resulted in a diagnosis of nocturnal paroxysmal dystonia, and he was started on baclofen, which has provided some, but not complete relief to nighttime symptoms. Parents are reporting he has more "good nights" than "bad nights," but "bad nights" come in stretches of a few days in length with no known trigger or relief.Most recently, X was evaluated by general genetics. Whole exome sequencing (WES) was pursued which revealed a pathogenic de novo variant in FBXO11 and provides a likely cause for his neurodevelopmental phenotype. However, he has some features not explained by FBX011; thus, reanalysis of his WES was performed and revealed a de novo variant of uncertain significance in RAF1. Because pathogenic variants in RAF1 have been associated with dilated cardiomyopathy and Noonan spectrum disorder, it was recommended that X be followed periodically in a cardiac genetics clinic. Family is well connected into the FBXO11 community, including supportive Facebook groups. Parents have shared that they do not feel X's breathing issues and pain fit with the phenotype of other children with FBXO11 mutations.X is also enrolled in a medical child care program to facilitate development and social-emotional functioning and receives learning, speech, occupational, physical, and feeding therapy while in attendance. Despite periods of absence due to contracting numerous viral illnesses over the past several months, X continues to make progress across developmental therapies and happily engages when at the program.What additional diagnostic tests and treatment should be considered to better understand X's medical and behavioral presentation? What are the implications of chronic sleep deprivation and stress on the behavior and development of infant with X's profile? What are important psychosocial considerations because it relates to children with medical complexity (CMC), particularly for X and his family to support caregiver, family, and X's quality of life and overall well-being?

Characterizing Opioid Prescribing Trends of Medical Oncologists From 2013 to 2019: Analysis From the Centers for Medicare & Medicaid Services Medicare Part D Prescribers Database.

PURPOSE: Opioid prescribing trends in medical oncology are poorly defined past 2017, the year after the CDC updated opioid prescription guidelines in noncancer settings. We aim to characterize pain management by medical oncologists by analyzing opioid and gabapentin prescribing trends from 2013 to 2019, identify physician-related factors associated with prescribing patterns, and assess whether CDC guidelines for nononcologic settings changed prescribing patterns. METHODS: The Centers for Medicare & Medicaid Services (CMS) Medicare Part D Prescribers-by Provider, CMS Medicare Part D Prescribers-by Provider and Drug, and CMS Medicare Physician National Downloadable files from 2013 to 2019 were merged by National Provider Identification. The database included physicians' sex, years of practice, regions, and practice settings. Multivariable binary logistic regression identified significant predictors of total opioid, long-acting opioid, and gabapentin prescriptions. RESULTS: Binary logistic regression modeling revealed no significant difference in mean daily total opioid prescriptions from 2013 to 2017. Daily opioid prescriptions by medical oncologists decreased significantly after 2017 (P < .001). Increased opioid prescribing was associated with physician male sex (P < .001), practicing over 10 years (P < .001), and practice in nonurban areas (P < .001). Opioid prescribing was greatest in the South and Midwest United States (P < .001). The same patterns were observed with total long-acting opioid prescriptions, whereas gabapentin prescribing increased from 2013 to 2019 (P < .001). CONCLUSION: Opioid prescriptions by medical oncologists decreased significantly from 2013 to 2019, but this decrease was most substantial from 2017 to 2019. These results may imply that the 2016 CDC guidelines influenced medical oncologists, particularly more junior physicians in urban settings, to manage chronic cancer pain with alternative therapies.

Common teratogenic medication exposures-a population-based study of pregnancies in the United States.

BACKGROUND: Risk mitigation for most teratogenic medications relies on risk communication via drug label, and prenatal exposures remain common. Information on the types of and risk factors for prenatal exposures to medications with teratogenic risk can guide strategies to reduce exposure. OBJECTIVE: This study aimed to identify medications with known or potential teratogenic risk commonly used during pregnancy among privately insured persons. STUDY DESIGN: We used the Merative™ MarketScan® Commercial Database to identify pregnancies with live or nonlive (ectopic pregnancies, spontaneous and elective abortions, stillbirths) outcomes among persons aged 12 to 55 years from 2011 to 2018. Start/end dates of medication exposure and pregnancy outcomes were identified via an adapted algorithm based on validation studies. We required continuous health plan enrollment from 90 days before conception until 30 days after the pregnancy end date. Medications with known or potential teratogenic risk were selected from TERIS (Teratogen Information System) and drug monographs based on the level of risk and quality of evidence (138 with known and 60 with potential risk). We defined prenatal exposure on the basis of ≥1 outpatient pharmacy claim or medical encounter for medication administration during target pregnancy periods considering medication risk profiles (eg, risk only in the first trimester or at a certain dose threshold). Sex hormones and hormone analogs, and abortion and postpartum/abortion hemorrhage treatments were not considered as teratogenic medications because of challenges in separating pregnancy-related indications, nor were opioids (because of complex risk-benefit considerations) or antiobesity medications if their only teratogenic mechanism was weight loss. RESULTS: Among all pregnancies, the 10 medications with known teratogenic risk and the highest prenatal exposures were sulfamethoxazole/trimethoprim (1988 per 100,000 pregnancy-years), high-dose fluconazole (1248), topiramate (351), lisinopril (144), warfarin (57), losartan (56), carbamazepine (50), valproate (49), vedolizumab (28 since 2015), and valsartan (25). Prevalence of exposure to sulfamethoxazole/trimethoprim decreased from 2346 to 1453 per 100,000 pregnancy-years from 2011 to 2018, but prevalence of exposure to vedolizumab increased 6-fold since its approval in 2015. Prenatal exposures in the first trimester were higher among nonlive pregnancies than among live-birth pregnancies, with the largest difference observed for warfarin (nonlive 370 vs live birth 78), followed by valproate (258 vs 86) and topiramate (1728 vs 674). Prenatal exposures to medications with potential teratogenic risk were most prevalent for low-dose fluconazole (6495), metoprolol (1325), and atenolol (448). The largest first-trimester exposure differences between nonlive and live-birth pregnancies were observed for lithium (242 vs 89), gabapentin (1639 vs 653), and duloxetine (1914 vs 860). Steady increases in hydralazine and gabapentin exposures were observed during the study years, whereas atenolol exposure decreased (561 to 280). CONCLUSION: Several medications with teratogenic risk for which there are potentially safer alternatives continue to be used during pregnancy. The fluctuating rates of prenatal exposure observed for select teratogenic medications suggest that regular reevaluation of risk mitigation strategies is needed. Future research focusing on understanding the clinical context of medication use is necessary to develop effective strategies for reducing exposures to medications with teratogenic risk during pregnancy.

Non-oestrogen-based and complementary therapies for menopause.

Women are living a significant portion of their adult lives in the post-reproductive phase, and many seek help for debilitating menopausal symptoms. Every individual's experience of menopausal transition is unique. Adopting a holistic approach to managing the menopause using a combination of lifestyle, hormonal, and non-hormonal interventions is key to maximise the quality of life of affected women. However, many opt to use non hormonal options or have contraindications to using hormonal therapy. Studies have shown that several pharmacological non-hormonal medications such as SSRIs, SSRI/SNRIs, Gabapentin, and Pregabalin are effective for managing vasomotor symptoms as well as other menopausal symptoms. Their main side effects are dry mouth, nausea, constipation, reduced libido, and loss of appetite. Clonidine is the only non-hormonal drug which is licenced for control of vasomotor symptoms in the UK, but has several side effects including dizziness and sleep disturbance. Cognitive Behavioural Therapy is recommended as a treatment for anxiety, sleep problems and vasomotor symptoms related to menopausal transition. Evidence for clinical efficacy and safety of herbal remedies and alternative therapies remains weak. Studies with neurokinin receptor 3 antagonists on women with hot flushes have shown improvement in vasomotor symptoms and results of large-scale studies are awaited.

Adverse drug events associated with nortriptyline compared with paroxetine and alternative medications in an older adult population: a retrospective cohort study in Southern California.

OBJECTIVE: Investigate risk for falls, fractures and syncope in older adult patients treated with nortriptyline compared with paroxetine and alternative medications. DESIGN: Retrospective cohort study. SETTING: The electronic medical record and prescription drug database of a large integrated healthcare system in Southern California. PARTICIPANTS: Ambulatory patients, age ≥65 years diagnosed with depression, anxiety disorder or peripheral neuropathy, dispensed one or more of ten study medications between 1 January 2008 and 31 December 2018. MAIN OUTCOME MEASURES: HR for falls, fractures and syncope with exposure to study medications adjusted for patient demographic variables and comorbidities. RESULTS: Among 195 207 subjects, 19 305 falls, 15 088 fractures and 11 313 episodes of syncope were observed during the study period. Compared with the reference medication, nortriptyline, the adjusted HRs (aHRs) for falls were statistically significantly greater for: paroxetine (aHR 1.48, 95% CI 1.39 to 1.57), amitriptyline (1.20, 95% CI 1.08 to 1.33), venlafaxine (1.44, 95% CI 1.34 to 1.56), duloxetine (1.25, 95% CI 1.12 to 1.40), fluoxetine (1.51, 95% CI 1.44 to 1.59), sertraline (1.53, 95% CI 1.44 to 1.62), citalopram (1.61, 95% CI 1.52 to 1.71) and escitalopram (1.37, 95% CI 1.21 to 1.54), but not gabapentin (0.95, 95% CI 0.89 to 1.02). For fractures, compared with nortriptyline, aHRs were significantly greater for: paroxetine, venlafaxine, duloxetine, fluoxetine, sertraline, citalopram, escitalopram and gabapentin, with aHRs ranging from 1.30 for gabapentin to 1.82 for escitalopram; risk was statistically similar for amitriptyline. For syncope, the aHRs were significantly greater for: paroxetine, venlafaxine, fluoxetine, sertraline and citalopram, with aHRs ranging from 1.19 for fluoxetine and paroxetine up to 1.30 for citalopram and sertraline; risk was similar for amitriptyline, duloxetine, escitalopram and gabapentin. CONCLUSIONS: Compared with therapeutic alternatives, nortriptyline was found to represent a lower risk for falls, fractures and syncope, versus comparator medications, except for a few instances that had equivalent risk. The risk for these adverse events from paroxetine was comparable to the alternative medications.

Association between chiropractic spinal manipulation and gabapentin prescription in adults with radicular low back pain: retrospective cohort study using US data.

OBJECTIVES: Radicular low back pain (rLBP) is often treated off-label with gabapentin or by chiropractors using chiropractic spinal manipulative therapy (CSMT). To date, no studies have examined the association between these interventions. We hypothesised that adults under 50 years of age receiving CSMT for newly diagnosed rLBP would have reduced odds of receiving a gabapentin prescription over 1 year-follow-up. DESIGN: Retrospective cohort study. SETTING: US network including linked medical records, medical claims and pharmacy claims of >122 million patients attending large healthcare organisations (TriNetX), queried 15 June 2023, yielding data from 2017 to 2023. PARTICIPANTS: Adults aged 18-49 were included at their first occurrence of rLBP diagnosis. Exclusions were severe pathology, other spinal conditions, on-label gabapentin indications and gabapentin contraindications. Propensity score matching controlled for variables associated with gabapentin use and receipt of prescription medication over the preceding year. INTERVENTIONS: Patients were divided into CSMT or usual medical care cohorts based on the care received on the index date of rLBP diagnosis. PRIMARY AND SECONDARY OUTCOME MEASURES: OR for gabapentin prescription. RESULTS: After propensity matching, there were 1635 patients per cohort (mean age 36.3±8.6 years, 60% women). Gabapentin prescription over 1-year follow-up was significantly lower in the CSMT cohort compared with the usual medical care cohort, with an OR (95% CI) of 0.53 (0.40 to 0.71; p<0.0001). Sensitivity analyses revealed early divergence in cumulative incidence of prescription; and no significant between-cohort difference in a negative control outcome (gastrointestinal medication) suggesting adequate control for pharmacological care preference. CONCLUSIONS: Our findings suggest that US adults receiving CSMT for newly diagnosed rLBP have significantly reduced odds of receiving a gabapentin prescription over 1-year follow-up compared with those receiving usual medical care. Results may not be generalisable and should be replicated in other healthcare settings and corroborated by a prospective study to reduce confounding.

Therapeutic Strategies for Postherpetic Neuralgia: Mechanisms, Treatments, and Perspectives.

PURPOSE OF REVIEW: Postherpetic neuralgia is an annoying pain that mainly affects older people. In order to give patients more options, this review summarizes the pharmacological and interventional treatments for postherpetic neuralgia and updates the research on the efficacy, thereby providing doctors with more treatment options. The adverse effects and effective doses of its various treatments are also presented so that the therapy can be prescribed according to their concrete physical conditions. In a word, this review is dedicated to providing a comprehensive overview of the treatment options for postherpetic neuralgia and offering patients more choices. RECENT FINDINGS: Combinational therapy is more excellent than monotherapy. The local anesthesia and gabapentin comprised outstanding compatibility. In addition, two therapeutic tools for PHN patients, especially for the intractable ones, electroacupuncture (EA), and osteopathic manipulative treatment (OMT), show their efficacy and become potential options to alleviate pain. In terms of treatment, guidelines recommend patients use tricyclic antidepressants (TCAs), gabapentin, pregabalin, and 5% lidocaine patches as the first-line medications, and gabapentin is investigated most, especially the gabapentin enacarbil (GEn). And drug efficacy can be limited by adverse effects and tolerated doses. Interventional treatments, with their invasiveness and operational difficulty, are usually considered for intractable patients. Combinational therapies may be used when a single therapy cannot achieve the desired effect. Therapies such as OMT and EA have also been proposed to palliate pain in some cases, and future directions of treatment may be investigated in Chinese medicine and acupuncture.

Prevalence of opioid and nonopioid pain management therapies among Medicare beneficiaries with musculoskeletal pain conditions from 2016 to 2019.

INTRODUCTION: Pain treatment guidelines prioritize nonopioid therapies over opioid medications to prevent opioid-related harms. We examined trends in receipt and intensity of nonpharmacologic, nonopioid medication, and opioid therapies among Medicare beneficiaries. METHODS: Using a 20% national random sample of Medicare data from 2016 to 2019, we identified fee-for-service beneficiaries with ≥2 diagnoses of back, neck, fibromyalgia, or osteoarthritis/joint pain annually. We excluded beneficiaries with cancer. We calculated annual proportions of beneficiaries who received physical therapy (PT), chiropractic care, gabapentin, and opioids, overall and in demographic, geographic, and clinical subgroups. We estimated the intensity of therapies using the annual number of visitsor prescription fills, prescription days' supply, and opioid dose. RESULTS: During 2016-2019, PT receipt increased (22.8% to 25.5%) and the mean number of visits among recipients of PT went from 12 to 13. Chiropractic receipt (~18%) and mean annual visits (~10) remained unchanged. The prevalence of gabapentin receipt was stable at ~22% and the mean annual number of fills was unchanged though gabapentin days increased slightly. Opioid prescribing decreased (56.7% to 46.5%) and reductions in opioid dose and duration were observed. Opioid receipt was high among beneficiaries who were under 65 years, American Indian/Alaska Native, Black/African American, or had opioid use disorder (OUD), in whom nonpharmacologic therapies were also received the least. CONCLUSION: Utilization of nonopioid therapies lagged opioids among Medicare beneficiaries with musculoskeletal pain, with limited changes from 2016 to 2019. As opioid prescribing declines and alternative pain therapy receipt remains low, there are potential increasing risks of pain going untreated or undertreated and individuals seeking illicit opioids to alleviate their pain.

Reasons for use and experiences of using phenibut, a mixed methods analysis of online reports.

Background: Phenibut is a drug similar in structure to gabapentin and pregabalin. It is available online without prescription, often marketed as a dietary supplement or amino acid derivative. Little is known about phenibut use despite its increased popularity in the United States over the last decade.Objective: To clarify reasons for taking phenibut, circumstances, and effects of use.Methods: Reports of phenibut, gabapentin, and pregabalin use were downloaded from a publicly-available database, Erowid.org. A mixed methods approach utilizing qualitative content analysis was used.Results: Of 229 reports, 211 were from male authors. People usually purchased phenibut online and reportedly used it for recreation, to manage a medical or psychiatric problem (primarily insomnia, anxiety), as a substitute for other drugs (especially benzodiazepines), to manage withdrawal from another substance (including benzodiazepines, opioids), and/or for performance enhancement. While it shared many reported effects with pregabalin and gabapentin such as anxiolysis, increased talkativeness, and impaired motor coordination, reports of gastrointestinal distress and sedation were more commonly attributed to phenibut. Several people reported difficulty in restricting their use and managing withdrawal.Conclusions: Phenibut reports suggest that phenibut may have some benefits for some people. Use also, however, carries risks of adverse effects, a potentially dangerous withdrawal syndrome, and addiction. Not dissimilar to unprescribed gabapentin or pregabalin, self-medication is a common motive for phenibut use. Physicians should continue to ask their patients about use of any non-prescribed medications, dietary supplements, or "amino acid derivatives."Abbreviation: PWUPh: people who use phenibut; PWUG: people who use gabapentin; PWUPr: people who use pregabalin.

Efficacy and Safety of Gabapentin in Improving Sleep Quality of Patients with Sensory Nervous System Diseases: A Meta-Analysis.

Context: Sensory nervous-system diseases are chronic diseases that injury or disease of the somatosensory nervous system causes. Sleep disorders usually accompany these diseases, and in turn, worsen their conditions and form a vicious circle that brings great difficulties in clinical treatment. Objective: The study intended to systematically evaluate the clinical efficacy and safety of gabapentin in improving the sleep quality of patients with sensory nervous-system diseases using a meta-analysis, so as to provide evidence-based medical evidence for clinical treatment. Design: The research team performed a comprehensive narrative review by searching the China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal (VIP), WANFANG, Chinese Biomedical Database (CBM), PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases. The search terms included gabapentin, 1-(aminomethyl)-cyclohexaneacetic acid, gabapentin hexal, gabapentin-ratiopharm, sleep, and insomnia. Setting: The review took place in the Department of Neurology at the First People's Hospital of Linping District in Hangzhou, China. Outcome Measures: The research team extracted the data from the studies meeting the inclusion criteria and then transferred them into the Review Manager 5.3 software for meta-analysis. The outcome measures included scores: (1) for the improvement in the degree of sleep interference score; (2) for the improvement in sleep quality; (3) for the rate of poor sleep quality; (4) for the rate awakenings of >5 per night; and (5) for the incidence of adverse reactions. Results: The research team found eight RCTs with 1269 participants, including 637 participants in a gabapentin test group and 632 participants in the placebo control group. The meta-analysis showed that the decrease in the degree of sleep interference [mean deviation (MD) = -0.86, 95% CI: (-0.91, -0.82), P < .00001] and the improvement in sleep quality [odds ratio (OR) = 2.64, 95% CI: (1.90, 3.67), P < .00001] in gabapentin group were significantly higher than those in placebo group (P < .05), while the rate of poor sleep quality [OR = 0.43, 95% CI: (0.23, 0.79), P = .007] and the rate of > 5 night awakenings [OR = 0.01, 95% CI: (0.05, 0.70), P = .01] in gabapentin group were significantly lower than those in placebo group (P < .05). No statistically significant differences existed in the incidence of adverse reactions between the two groups. Conclusions: Gabapentin is safe and effective in improving the sleep quality of patients with sensory nervous-system diseases. Due to the limitations of sample size and types of diseases in the current study, the field needs multicenter, large-sample, and high-quality RCTs for further validation in the future.

Comparison the effect of valerian and gabapentin on RLS and sleep quality in hemodialysis patients: A randomized clinical trial.

INTRODUCTION: This study aimed to compare the effect of valerian and gabapentin on restless legs syndrome (RLS) and sleep quality in HD patients. METHODS: In this cross over clinical trial study, 40 HD patients allocated into a valerian and gabapentin group. In the first phase of the study, Group A received valerian and Group B received gabapentin 1 h before bedtime for 1 month. In the second phase, the two groups' treatment regimen was swapped. After a 1-month washout period, the same process was repeated on the crossover groups. RESULTS: After the first phase, the mean score of RLS was lower in the gabapentin group. But there was no statistically significant difference between the two groups in terms of sleep quality score before and after the first and second interventions. CONCLUSION: Gabapentin is more effective than valerian in improving RLS, but both are equally effective in improving sleep quality.

Comparative Efficacy of Adjuvant Nonopioid Analgesia in Adult Cardiac Surgical Patients: A Network Meta-Analysis.

OBJECTIVES: To compare the relative efficacy of adjuvant nonopioid analgesic regimens in adult cardiac surgical patients. DESIGN: This frequentist, random-effects network meta-analysis (NMA) was prospectively registered on PROSPERO (CRD42021282913) and conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses for Network Meta-Analyses (PRISMA-NMA). The risk of bias (RoB) and confidence of evidence were assessed by RoB 2 and Confidence in Network Meta-Analysis, respectively. Relevant databases were searched from inception to October 9, 2021. SETTING: A total of 124 (N = 26,257) randomized controlled trials were included, of which 110 were analyzed. PARTICIPANTS: Trials enrolling adults (≥18 years of age) undergoing cardiac surgery that compared nonopioid analgesics against other nonopioid analgesics, placebo, or no additional treatment, as adjuvants to standard analgesic management, and reported at least 1 of the outcomes of interest. MEASUREMENT AND MAIN RESULTS: Outcomes of interest included resting postoperative pain scores at 24 hours. Compared with standard care and/or placebo, pain scores were reduced significantly by 10 different regimens, including acetaminophen (N = 176; mean difference [MD] -0.66 points, 95% CI -1.16 to -0.15 points; high confidence), magnesium (N = 323; -0.05 points, 95% CI -0.07 to -0.02 points; high confidence), gabapentin (N = 96; MD -0.40 points, 95% CI -0.71 to -0.09; moderate confidence), and clonidine (N = 64; MD v0.38 points, 95% CI -0.73 to v0.04 points; moderate confidence). Indomethacin, diclofenac, magnesium, and gabapentin significantly reduced 24-hour opioid consumption. Four regimens significantly decreased the intensive care unit length of stay. Hydrocortisone, dexmedetomidine, and clonidine significantly decreased the duration of mechanical ventilation. Magnesium decreased, while methylprednisolone significantly increased, the risk of myocardial infarction. CONCLUSIONS: Given the increasing emphasis on enhanced recovery after surgery(ERAS) protocols and the eventual goal of limiting opiate prescriptions postoperatively, the authors' data suggested far greater use of nonopioid adjuncts to minimize pain and enhance recovery following cardiac surgery.

Outpatient Treatment With Gabapentin in Women With Severe Acute Pain After Cesarean Delivery Is Ineffective: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Most of the 1.1 million women who deliver by cesarean in the United States each year have an uncomplicated recovery. However, severe pain resistant to standard multimodal therapy within the first days after surgery is associated with an increased risk for prolonged pain and opioid use. The best outpatient management for parturients with severe resistant early onset pain is not known. METHODS: We performed a prospective, double-blind, placebo-controlled, randomized trial of up to 12 weeks of outpatient treatment with gabapentin to evaluate its effectiveness to facilitate opioid cessation in women with at least 2 reports of severe pain during the immediate postpartum period resistant to standard multimodal pain management. Time to opioid cessation was the primary outcome. Time to pain resolution; time to discontinuation of gabapentin, acetaminophen, and ibuprofen; time to self-reported recovery; and National Institute of Health Patient-Reported Outcomes System (PROMIS) surveys for anxiety, depression, fatigue, and physical function were assessed as secondary outcomes. RESULTS: There was no difference in time to opioid cessation between patients who were randomly assigned to be treated with gabapentin (Kaplan-Meier estimated median of 2 [25th-75th percentiles of 1-3] weeks, n = 35) versus those who were treated with placebo (2 [1-3] weeks, n = 35). The hazard ratio was 1.1 (95% confidence interval [CI], 0.67-1.8), P = .65. There were no differences in any secondary end points between the study groups. CONCLUSIONS: Outpatient supplementation with gabapentin did not reduce time to opioid cessation, pain, anxiety, depression, fatigue, or improve physical function in women with severe pain after cesarean delivery. Gabapentin should not be routinely added to the standard outpatient multimodal regimen of ibuprofen, acetaminophen, and opioids.

A Narrative Review of the Lesser Known Medications for Treatment of Restless Legs Syndrome and Pathogenetic Implications for Their Use.

Background: There are several well-known treatments for Restless Legs Syndrome (RLS), including dopamine agonists (pramipexole, ropinirole, rotigotine), anticonvulsants (gabapentin and its analogs, pregabalin), oral or intravenous iron, opioids and benzodiazepines. However, in clinical practice, treatment is sometimes limited due to incomplete response or side effects and it is necessary to be aware of other treatment options for RLS, which is the purpose of this review. Methods: We performed a narrative review detailing all of the lesser known pharmacological treatment literature on RLS. The review purposefully excludes well-established, well-known treatments for RLS which are widely accepted as treatments for RLS in evidence-based reviews. We also have emphasized the pathogenetic implications for RLS of the successful use of these lesser known agents. Results: Alternative pharmacological agents include clonidine which reduces adrenergic transmission, adenosinergic agents such as dipyridamole, glutamate AMPA receptor blocking agents such as perampanel, glutamate NMDA receptor blocking agents such as amantadine and ketamine, various anticonvulsants (carbamazepine/oxcarbazepine, lamotrigine, topiramate, valproic acid, levetiracetam), anti-inflammatory agents such as steroids, as well as cannabis. Bupropion is also a good choice for the treatment of co-existent depression in RLS because of its pro-dopaminergic properties. Discussion: Clinicians should first follow evidence-based review recommendations for the treatment of RLS but when the clinical response is either incomplete or side effects are intolerable other options can be considered. We neither recommend nor discourage the use of these options, but leave it up to the clinician to make their own choices based upon the benefit and side effect profiles of each medication.

Case Series: Synergistic Effect of Gabapentin and Adjuvant Pregabalin in Neuropathic Pain.

Gabapentin and pregabalin both exert high affinity to the α2δ subunit of the voltage-gated calcium channels which inhibits excitatory neurotransmitter release. The synergistic mechanism was described in rats given combinations of gabapentin and pregabalin. In this case series, we described 2 cases which may illustrate the synergistic effect of gabapentin and pregabalin in treatment resistant neuropathic pain. Low dose pregabalin was added to therapeutic gabapentin to achieve appreciable pain reduction in one case and improved quality of life in another case. Further research with more enrollment and longer study duration may help elucidate the appropriate dosing and potential associated side effects.

Observation and Analysis of Clinical Efficacy of Zhuang Medicine Lotus Acupuncture Cupping Stasis Therapy on Patients with Postherpetic Neuralgia.

OBJECTIVE: To explore the clinical efficacy of Zhuang Medicine Lotus Acupuncture Cupping Stasis Therapy on patients with postherpetic neuralgia (PHN) and its action mechanism. METHODS: 36 patients are randomly divided into Lotus Acupuncture Cupping Stasis Therapy group, pure cupping group and gabapentin group, with a total of five observation points for the first, fifth, tenth, fifteenth, and twentieth sessions of therapy (one session every three days). At each observation point, the venous blood of the patients is taken, and the contents of and changes in WNT3a, Frizzled8, ß-catenin, IL-18, TNF-α, NR2B, NK-1 and SP are tested by ELISA, RT-PCR and WesternBlot, respectively. The VAS scores and safety of the patients in the three groups are compared. RESULTS: With increased time spent in therapy, the VAS scores of patients in each group decreased gradually and there was a significant reduction in pain in patients in the Lotus Acupuncture Cupping Stasis Therapy group compared to the gabapentin and pure cupping groups (P<0.05). The levels of IL-18, TNF-α, NK-1, SP, WNT3a, Frizzled 8 and ß-catenin in the serum of all patients experienced a constant decline over time (P<0.05); the levels of the aforesaid factors in the serum of patients in the Lotus Acupuncture Cupping Stasis Therapy group dropped remarkably after the tenth session of therapy compared to those in gabapentin and pure cupping groups (P<0.05). CONCLUSIONS: Zhuang Medicine Lotus Acupuncture Cupping Stasis Therapy can significantly reduce the pain of PHN patients, with a good therapeutic effect, and it is worthy of clinical use.

Exploration of restless legs syndrome under the new concept: A review.

Restless leg syndrome (Restless legs syndrome, RLS) is a common neurological disorder. The pathogenesis of RLS remains unknown, and recent pathophysiological developments have shown the contribution of various genetic markers, neurotransmitter dysfunction, and iron deficiency to the disease, as well as other unidentified contributing mechanisms, particularly chronic renal dysfunction. RLS enhancement syndrome is frequently observed in patients with RLS who have received long-term dopamine agonist therapy, manifesting as a worsening of RLS symptoms, usually associated with an increase in the dose of dopamine agonist. Some patients with RLS can adequately control their symptoms with non-pharmacological measures such as massage and warm baths. First-line treatment options include iron supplementation for those with evidence of reduced iron stores, or gabapentin or pregabalin, as well as dopamine agonists, such as pramipexole. Second-line therapies include opioids such as tramadol. RLS seriously affects the quality of life of patients, and because its pathogenesis is unclear, more biological evidence and treatment methods need to be explored.

Efficacy and safety of different antidepressants and anticonvulsants in central poststroke pain: A network meta-analysis and systematic review.

OBJECTIVE: To evaluate the efficacy and safety of different antidepressants and anticonvulsants in the treatment of central poststroke pain (CPSP) by network meta-analysis and provide an evidence-based foundation for clinical practice. METHODS: PubMed, Cochrane Library, EMBASE, CNKI, APA PsycINFO, Wanfang, VIP and other databases were searched by computer to find clinical randomized controlled studies (RCTs) on drug treatment of CPSP. The retrieval time limit was from the establishment of each database to July 2022. The quality of the included RCTs was evaluated using the bias risk assessment tool recommended by Cochrane. Stata 14.0 was used for network meta-analysis. RESULTS: A total of 13 RCTs, 1040 patients and 9 drugs were finally included. The results of the network meta-analysis showed that the effectiveness ranking as rated by the visual analog scale (VAS) was gabapentin > pregabalin > fluoxetine > lamotrigine > duloxetine > serqulin > amitriptyline > carbamazepine > vitamin B. Ranking according to the numerical rating scale (NRS) was pregabalin > gabapentin > carbamazepine. Ranking derived from the Hamilton depression scale (HAMD) was pregabalin > duloxetine > gabapentin > amitriptyline. CONCLUSION: All nine drugs can relieve the pain of CPSP patients to different degrees; among them pregabalin and gabapentin have the most significant effect, and gabapentin and pregabalin also have the most adverse reactions. In the future, more multicenter, large sample, double-blind clinical randomized controlled trials need to be carried out to supplement and demonstrate the results of this study.

Treatment modalities in brachioradial pruritis: a systematic review.

INTRODUCTION: Brachioradial pruritis is a rare dysesthesia syndrome that is known to negatively impact quality of life. No consensus exists regarding optimal treatment strategies. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Collaboration Clinical Trials Registry from 1966 to 2021 for studies using the title word "brachioradial pruritis" with no language restriction. One author (A.Z.) screened and performed full article reviews of all randomized clinical trials, cohort studies, case-control studies, case reports, and case series describing treatment outcomes among patients with brachioradial pruritis. RESULTS: We identified 239 potential articles with a final set of 45 articles meeting inclusion criteria. Only a single randomized clinical trial was identified, finding no significant benefit of topical capsaicin cream. Treatment modalities with the greatest number of reported successful therapeutic trials include gabapentin and tricyclic antidepressants. In patients with confirmed cervical spine disease, spine-directed therapies such as epidural injections were found to be beneficial. Case reports and small case series describing less-common treatments were also identified. DISCUSSION: The literature is overall limited with the greatest support for gabapentin, pregabalin, tricyclic antidepressants, and spine-directed therapies in appropriate patients with brachioradial pruritis. Future randomized clinical trials are needed to compare the relative effectiveness of available treatments.

The interplay of epilepsy with impaired mitophagy and autophagy linked dementia (MAD): A review of therapeutic approaches.

The duration and, age of dementia have been linked to a higher risk of seizures. The exact mechanism that drives epileptogenesis in impaired mitophagy and autophagy linked dementia (MAD) is fully defined after reviewing the Scopus, Publon, and Pubmed databases. The epileptogenesis in patients with Alzheimer's disease dementia (ADD) and Parkinson's disease dementia (PDD) is due to involvement of amyloid plaques (Aß), phosphorylated tau (pTau), Parkin, NF-kB and NLRP3 inflammasome. Microglia, the prime protective and inflammatory cells in the brain exert crosstalk between mitophagy and inflammation. Several researchers believed that the inflammatory brain cells microglia could be a therapeutic target for the treatment of a MAD associated epilepsy. There are conventional antiepileptic drugs such as gabapentin, lamotrigine, phenytoin sodium, carbamazepine, oxcarbazepine, felbamate, lamotrigine, valproate sodium, and topiramate are prescribed by a psychiatrist to suppress seizure frequency. Also, the conventional drugs generate serious adverse effects and synergises dementia characteristics. The adverse effect of carbamazepine is neurotoxic and also, damages haemopoietic system and respiratory tract. The phenytoin treatment causes cerebellar defect and anemia. Dementia and epilepsy have a complicated relationship, thus targeting mitophagy for cure of epileptic dementia makes sense. Complementary and alternative medicine (CAM) is one of the rising strategies by many patients of the world, not only to suppress seizure frequency but also to mitigate dementia characteristics of patients. Therefore our present review focus on the interplay between epilepsy and MAD and their treatment with CAM approaches.