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Alcohol use disorder (AUD) is a devastating illness for which effective treatments are lacking. Studies over the last two decades have shown that baclofen, aGABA-B agonist, could be a promising treatment for AUD. However, the efficacy of baclofen is still controversial, and studies have shown that itmay be associated with an excess of hospitalizations and deaths. In March 2014, the French Health Safety Agency granted a "Temporary Recommendation for Use" (TRU) regulating the prescription of baclofen in subjects with AUD. The TRU allowed physicians to prescribe high-dose baclofen (up to 300 mg/d). The doses were adjusted, and tailored to the needs of each patient. Between March 2014 and March 2017, TRU clinical data were collected for a total of 6,939 subjects. The recorded data included information on alcohol consumption, the intensity of alcohol cravings, and adverse events. The present article proposes an analysis of the data provided by the TRU. Subjects for which data were missing regarding baclofen daily dosage, alcohol consumption or craving scores were discarded from the analyses. A cohort of two groups of subjects was analyzed. The first group included all TRU subjects suitable for analyses (5,550 subjects), and the second group included subjects followed for at least 365 days (169 subjects). Comparisons weremade between baseline and endpoint of the follow-up period. The results show that a majority of subjects in the whole cohort had received doses of over 80 mg/d. The mean dose of baclofen at the endpoint was >110 mg/d in the second group of subjects. Doses of >80 mg/d were not associated with an increase in adverse events after adjustment for the follow-up duration. In terms of efficacy, comparisons between baseline and endpoint show that baclofen treatment significantly decreased alcohol consumption and alcohol cravings, and significantly increased the number of subjects with null or low-risk alcohol consumption according to WHO criteria. [ABSTRACT FROM AUTHOR]

Alcohol use disorder (AUD) is a devastating illness for which effective treatments are lacking. Studies over the last two decades have shown that baclofen, a GABA-B agonist, could be a promising treatment for AUD. However, the efficacy of baclofen is still controversial, and studies have shown that it may be associated with an excess of hospitalizations and deaths. In March 2014, the French Health Safety Agency granted a “Temporary Recommendation for Use” (TRU) regulating the prescription of baclofen in subjects with AUD. The TRU allowed physicians to prescribe high-dose baclofen (up to 300 mg/d). The doses were adjusted, and tailored to the needs of each patient. Between March 2014 and March 2017, TRU clinical data were collected for a total of 6,939 subjects. The recorded data included information on alcohol consumption, the intensity of alcohol cravings, and adverse events. The present article proposes an analysis of the data provided by the TRU. Subjects for which data were missing regarding baclofen daily dosage, alcohol consumption or craving scores were discarded from the analyses. A cohort of two groups of subjects was analyzed. The first group included all TRU subjects suitable for analyses (5,550 subjects), and the second group included subjects followed for at least 365 days (169 subjects). Comparisons were made between baseline and endpoint of the follow-up period. The results show that a majority of subjects in the whole cohort had received doses of over 80 mg/d. The mean dose of baclofen at the endpoint was >110 mg/d in the second group of subjects. Doses of >80 mg/d were not associated with an increase in adverse events after adjustment for the follow-up duration. In terms of efficacy, comparisons between baseline and endpoint show that baclofen treatment significantly decreased alcohol consumption and alcohol cravings, and significantly increased the number of subjects with null or low-risk alcohol consumption according to WHO criteria.

Medication-induced central sleep apnea (CSA) is one of the eight categories of causes of CSA but in the absence of awareness and careful history may be misclassified as primary CSA. While opioids are a well-known cause of respiratory depression and CSA, non-opioid medications including sodium oxybate, baclofen, valproic acid, gabapentin, and ticagrelor are less well-recognized. Opioids-induced respiratory depression and CSA are mediated primarily by µ-opioid receptors, which are abundant in the pontomedullary centers involved in breathing. The non-opioid medications, sodium oxybate, baclofen, valproic acid, and gabapentin, act upon brainstem gamma-aminobutyric acid (GABA) receptors, which co-colonize with µ-opioid receptors and mediate CSA. The pattern of ataxic breathing associated with these medications is like that induced by opioids on polysomnogram. Finally, ticagrelor also causes periodic breathing and CSA by increasing central chemosensitivity and ventilatory response to carbon dioxide. Given the potential consequences of CSA and the association between some of these medications with mortality, it is critical to recognize these adverse drug reactions, particularly because discontinuation of the offending agents has been shown to eliminate CSA., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Spasticity and dystonia are movement impairments that can occur in childhood-onset neurological disorders. Severely affected individuals can be treated with intrathecal baclofen (ITB). Concomitant use of ITB and opioids has been associated with central nervous system (CNS) depression. This study aims to describe the clinical management of this interaction, based on a case series and review of literature., Methods: Four individuals with childhood-onset CNS disorders (age 8-24) and CNS-depressant overdose symptoms after the concomitant use of ITB and opioids are described. The Drug Interaction Probability Scale (DIPS) was calculated to assess the cause-relationship (doubtful <2, possible 2-4, probable 5-8, and highly probable >8) of the potential drug-drug interaction. A literature review of similar previously reported cases and the possible pharmacological mechanisms of opioid-baclofen interaction is provided., Results: After ITB and opioid co-administration, three out of four patients had decreased consciousness, and three developed respiratory depression. DIPS scores indicated a possible cause-relationship in one patient (DIPS: 4) and a probable cause-relationship in the others (DIPS: 6, 6, and 8). Discontinuation or adjusting ITB or opioid dosages resulted in clinical recovery. All patients recovered completely. In the literature, two articles describing nine unique cases were found., Conclusion: Although the opioid-ITB interaction is incompletely understood, concomitant use may enhance the risk of symptoms of CNS-depressant overdose, which are potentially life-threatening. If concomitant use is desirable, we strongly recommend to closely monitor these patients to detect interaction symptoms early. Awareness and monitoring of the potential opioid-ITB interaction is essential to reduce the risk of severe complications., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Objective: Intrathecal baclofen (ITB) pumps are commonly used in pediatric patients with cerebral palsy (CP) and medically refractory spasticity. However, catheter malfunction and associated risk factors are not well understood. The aim of this study was to examine potential risk factors for spinal catheter malfunction and characterize postoperative follow-up to understand the clinical consequences., Methods: Patients who received ITB pump replacement or revision at Boston Children's Hospital between 2010 and 2023 were retrospectively reviewed. The spinal catheter revision cohort (SCRC) included patients whose spinal catheter was occluded requiring lumbar catheter revision. The second cohort included abdominal pump replacements only (APRC). Between-group comparisons and multivariable regression identified factors associated with catheter revision and postoperative outcomes., Results: Forty-one (33.6%) patients underwent spinal catheter revision and were compared with 81 patients (66.4%) who underwent abdominal pump replacement only. Younger age at surgery and an elevated preoperative lower-extremity modified Ashworth scale grade were associated with spinal catheter revision (p < 0.05). Catheter model type, tip location, and history of spinal fusion were not associated with obstruction. Postoperatively, SCRC patients experienced a higher rate of infection (17.1%) relative to APRC patients (0%) within 30 days from their ITB pump replacement procedure (p < 0.05) and greater likelihood of subsequent ITB system removal compared with the APRC (24.4% vs 7.4%, p < 0.05). Although not differing preoperatively, SCRC patients had lower postoperative ITB doses when compared with the APRC group (median dose 143 vs 350 µg/day, p < 0.05) at hospital discharge and remained statistically different at the 6-month and 1-year follow-ups (p < 0.05). There were no postoperative differences in baclofen overdose, withdrawal, or median number of hospital readmissions within 30 days. Overall, 31.7% of spinal catheter revisions were unanticipated by the clinical team at time of surgery., Conclusions: Younger age at surgery and increased preoperative lower-extremity tone may be risk factors for catheter obstruction, resulting in a higher rate of postoperative infection and subsequent ITB pump removal compared with pump replacement alone. Spinal catheter occlusion can complicate revision or replacement procedures, especially when unanticipated. Routine clinical assessment may be inadequate for diagnosing insidious catheter malfunction. Catheter occlusion deserves further study, and routine assessment of catheter patency may be warranted to prevent suboptimal tone therapy.

Objective: The aim of this study was 1) to describe the rate of intrathecal baclofen (ITB)-associated complications at a large tertiary center, and 2) to evaluate the impact of patient-related factors on the likelihood of developing such complications., Methods: A retrospective single-center study was carried out. A total of 301 eligible patients were included in the analysis. Univariate regression models were used to evaluate the impact of age, sex, diagnosis, ambulation status, modified Ashworth scale score, body mass index, diabetes status, and pain level on the likelihood of developing a device-related infection, pump malfunction, catheter malfunction, and other clinically significant complications., Results: Overall, 27% of patients experienced an ITB-related complication. The most common complications included infection (6%, 18/301), pump malfunction (7.3%, 22/301), and catheter malfunction (14%, 42/301). The univariate analyses revealed that the patient's ambulatory status had a significant impact on the likelihood of developing a catheter-related malfunction. Furthermore, a trend toward significance was identified between patients' preoperative body mass index and device-related infection. Finally, the risk of suffering any ITB-related complications was statistically correlated with the number of years that had passed since the initial pump implantation., Conclusions: The authors' analysis reveals a previously underrecognized association between ambulatory status at the time of ITB pump implantation and the incidence of catheter-related complications, and confirms the impact of time since surgery on the risk of developing any ITB-related complication. The patient's age, sex, diagnosis, diabetes status, or pain level at baseline were not associated with the risk of complications. Collectively, these insights contribute novel information to the existing literature, providing practical value for physicians in guiding patient selection for ITB therapy.

Background: Gamma hydroxybutyrate (GHB) is used illicitly for its sedative hypnotic effects, and those who take it regularly are at risk of developing a substance use disorder. Withdrawal from GHB can include severe symptoms that may require medical management. For GHB use and withdrawal during pregnancy, there are no evidence- or practice-based guidelines to follow, and there is only minimal research literature., Case Summary: We present the case of a 32-year-old woman, G1P0 at 29 weeks and 6 days of gestation, admitted to the perinatal unit at a tertiary hospital for GHB withdrawal management and stabilization. GHB withdrawal was managed with a combination of baclofen and diazepam. We report the dosing and tapering of these medications throughout her 14-day admission. Withdrawal symptoms were well managed with this medication protocol, and she did not experience any features of complicated withdrawal. The patient later presented to hospital in preterm labor and precipitously delivered a healthy, preterm infant male at 34 weeks and 5 days of gestation. At 7 months postpartum, the patient continued to engage with perinatal addiction service, reported no use of GHB since her admission, and was parenting her healthy son., Clinical Significance: There is a paucity of guidelines for managing GHB withdrawal in pregnancy. This case demonstrates good clinical outcomes administering a short-term combination of diazepam and baclofen during the third trimester of pregnancy. This case helps to fill a gap in the literature and may inform future research or clinical decision-making in similar situations., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 American Society of Addiction Medicine.)

Objective: This review highlights adverse effects of baclofen and tizanidine in older community-dwelling adults., Data Sources: A literature search was conducted, including search terms of "adverse effect," "baclofen," "elderly," "falls," "fractures," and "tizanidine." Studies were included if they described community-dwelling adults aged 50 years and older who received oral baclofen or tizanidine. The Federal Drug Administration Adverse Event Reporting System (FAERS) data were compiled for adverse effect incidence., Study Selection and Data Extraction: The literature search was completed in July 2019 and updated in June 2023. Reviews performed by 2 independent reviewers yielded 15 records. FAERS identified 486 (baclofen) and 305 (tizanidine) adverse effects of interest., Data Synthesis: Two retrospective cohort studies evaluating baclofen use in older adults showed increased hospitalizations for encephalopathy in chronic kidney disease (7.2% vs 0.1%) and end-stage renal disease (daily dose 20 mg or more; relative risk [RR] 19.8, 95% CI = [14.0-28.0]). Other articles were case reports; 10 articles reported dyskinesias, encephalopathy or disorientation, and drowsiness associated with baclofen, and 5 articles reported bradycardia and/or hypotension with tizanidine. The FAERS Public Dashboard revealed 12.1% and 28.7% overall incidence of adverse effects of interest, with a 27.8% and 29.2% incidence of falls for baclofen and tizanidine, respectively. Baclofen and tizanidine are associated with concerning adverse effects in older adults. Alternative agents should be considered, but, if necessary, providers should start at lower doses and increase slowly., Conclusions: This review highlights the importance of using baclofen and tizanidine with caution in older adults., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: We studied physicians' opinions and experiences concerning clinical concerns, perceived severity, occurrence, and management of baclofen withdrawal due to abrupt discontinuation.Methods: A nationwide 26-question electronic survey was distributed via e-mail to physicians (N = 952) representing varying specialties who manage spasticity with baclofen. A total of 110 physicians provided responses to the survey (response rate = 11.6%). Results were evaluated using descriptive statistics.Results: Withdrawal from both oral and intrathecal (IT) baclofen was recognized as a significant concern and was observed by most respondents. However, approximately 75% and 35% of respondents or their clinic sites lack established management protocols for managing anticipated interruption of oral or IT baclofen, respectively.Conclusions: These findings highlight the need for further research on and the development of guidelines for the prevention and treatment of baclofen withdrawal. The results of this survey, along with a systematic literature review and multidisciplinary stakeholder input, may be helpful in establishing guidelines for the treatment and prevention of baclofen withdrawal. [ABSTRACT FROM AUTHOR]

Aims: Post-lumbar puncture headache occurs in 5% to 12% of children. The purpose of this study was to determine the frequency and predictors of post-lumbar puncture headache in children with hypertonia undergoing lumbar puncture for intrathecal baclofen trial. Methods: This was a retrospective single-center review of all 43 children (<18 years) with hypertonia and/or dyskinesia undergoing intrathecal baclofen trial from 2013-2022. Predictors of post-lumbar puncture headache were evaluated via 2-way paired t test and Fisher exact test. Results: Seven subjects (16.3%) developed post-lumbar puncture headache. Of patients who developed post-lumbar puncture headache, 3 required emergency care or hospitalization. One was misdiagnosed with constipation. The 16 patients without opening pressure measured were excluded from subsequent analyses. Of the 27 patients with documented opening pressure, the mean opening pressure was 24.0 cm H 2 O (SD 6.5) and 5 (18.5%) had elevated opening pressure (>28 cm H 2 O). Mean opening pressure was higher for those with post-lumbar puncture headache (28.6 vs 22.4 cm H 2 O, P  = .014). Sixty percent of patients with elevated opening pressure developed post-lumbar puncture headache. Baclofen pumps were placed in 4 (80%) patients with elevated opening pressure and 6 (85.7%) with post-lumbar puncture headaches without complications. Interpretation: The risk of post-lumbar puncture headache after intrathecal baclofen trial was higher than reported in the literature, likely because of greater rates of elevated opening pressure. Physicians may use opening pressure to predict risk for post-lumbar puncture headache and should educate families about symptoms. Elevated opening pressure or post-lumbar puncture headache may not preclude baclofen pump placement., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To assess the complication risks associated with intrathecal baclofen (ITB) pumps in cerebral palsy (CP) patients undergoing posterior spinal fusion (PSF) and to determine if timing of pump implantation before or during PSF impacts the risk of complications., Methods: A prospectively collected multicenter database was retrospectively reviewed to identify CP patients undergoing PSF from 2008 to 2023. Patients were divided into 2 cohorts: those with an ITB pump (ITB cohort) and those without (non-ITB cohort). The ITB cohort was further categorized by placement of the pump prior to or during PSF. Cohorts were then compared in terms of postoperative complications, perioperative complications, and need for revision surgery., Results: Four hundred six patients (ITB n = 79 [53 prior to, 26 during PSF], non-ITB n = 326) were included in this analysis. At an average follow-up of 4.0 years (range 2-10 years), there were no significant differences between the ITB and non-ITB cohorts in the rate of perioperative complications (5.0% vs 6.5%, p = 0.80), revision surgeries (2.5% vs 4.6%, p = 0.54), or any complication type, regardless of whether pumps were placed prior to or during PSF, aside from longer surgical times in the latter group., Conclusion: Complication rates are similar for ITBs placed prior to and during PSF. Patients with spastic CP may safely be treated with ITB pumps without increased risks of complication or further reoperation/revision following PSF., Level of Evidence: Level III., (© 2023. The Author(s), under exclusive licence to Scoliosis Research Society.)

Aims: To address the question of tailored baclofen prescribing in alcohol use disorder (AUD) in relation to dose-dependent efficacy and the potential danger of high doses and to provide suggestions for the use of high doses of baclofen in the treatment of AUD. The context is the approvement in France of baclofen in the treatment of AUD without dose limitation, making French physicians, who usually prescribe baclofen in a tailored manner, often use high or very high doses., Methods: A narrative review of the results of randomized controlled trials (RCTs) and observational studies that used tailored baclofen prescribing and of the severe adverse effects of baclofen that have been reported in the literature., Results: The results show that RCTs using tailored doses of baclofen in AUD are not completely demonstrative, though they are encouraging according to certain meta-analyses, while observational studies that used tailored doses constantly show a good effectiveness of baclofen treatment. The results suggest that many severe adverse effects of baclofen could be related to a nonrespect by physicians of prescription rules and appropriate treatment monitoring., Conclusions: The use of tailored doses shows that the dose required to suppress cravings is highly variable, low or high, depending on each case. Analysis of the circumstances in which severe adverse effects occur suggest that a careful monitoring of baclofen prescribing might prevent a large majority of severe adverse effects. We propose that the education of the patients and the prescription skills, seriousness, and availability of the prescribing physicians are of major importance in the managing of tailored baclofen treatment of AUD., (© The Author(s) 2024. Medical Council on Alcohol and Oxford University Press.)

Background: The growth of oral muscle relaxant prescriptions among older adults in the United States is concerning due to the drugs' adverse sedative effects. Baclofen is a gamma-aminobutyric acid agonist muscle relaxant that is associated with encephalopathy. We characterized the risk of fall and fracture associated with oral baclofen against other muscle relaxants (tizanidine or cyclobenzaprine) in older adults., Methods: We designed a new-user, active-comparator study using tertiary health system data from Geisinger Health, Pennsylvania (January 2005 through December 2018). Older adults (aged ≥65 years) newly treated with baclofen, tizanidine, or cyclobenzaprine were included. Propensity score-based inverse probability of treatment weighting (IPTW) was used to balance the treatment groups on 58 baseline characteristics. Fine-Gray competing risk regression was used to estimate the risk of fall and fracture., Results: The study cohort comprised of 2205 new baclofen users, 1103 new tizanidine users, and 9708 new cyclobenzaprine users. During a median follow-up of 100 days, baclofen was associated with a higher risk of fall compared to tizanidine (IPTW incidence rate, 108.4 vs. 61.9 per 1000 person-years; subdistribution hazard ratio [SHR], 1.68 [95% CI, 1.20-2.36]). The risk of fall associated with baclofen was comparable to cyclobenzaprine (SHR, 1.17 [95% CI, 0.93-1.47]) with a median follow-up of 106 days. The risk of fracture was similar among patients treated with baclofen versus tizanidine (SHR, 0.85 [95% CI, 0.63-1.14]) or cyclobenzaprine (SHR, 0.85 [95% CI, 0.67-1.07])., Conclusions: The risk of fall associated with baclofen was greater than tizanidine, but not compared to cyclobenzaprine in older adults. The risk of fracture was comparable among the older users of baclofen, tizanidine, and cyclobenzaprine. Our findings may inform risk-benefit considerations in the increasingly common clinical encounters where oral muscle relaxants are prescribed., (© 2023 The American Geriatrics Society.)

Study Design: Retrospective, single-center, cohort study., Objective: Investigate whether the incidence of postoperative delirium in older adults undergoing spinal fusion surgery is associated with postoperative muscle relaxant administration., Summary of Background Data: Baclofen and cyclobenzaprine are muscle relaxants frequently used for pain management following spine surgery. Muscle relaxants are known to cause central nervous system side effects in the outpatient setting and are relatively contraindicated in individuals at high risk for delirium. However, there are no known studies investigating their side effects in the postoperative setting., Methods: Patients over 65 years of age who underwent elective posterior lumbar fusion for degenerative spine disease were stratified into two treatment groups based on whether postoperative muscle relaxants were administered on postoperative day one as part of a multimodal analgesia regimen. Doubly robust inverse probability weighting with cox regression for time-dependent covariates was used to examine the association between postoperative muscle relaxant use and the risk of delirium while controlling for variation in baseline characteristics., Results: The incidence of delirium was 17.6% in the 250 patients who received postoperative muscle relaxants compared with 7.9% in the 280 patients who did not receive muscle relaxants ( P=0.001 ). Multivariate analysis to control for variation in baseline characteristics between treatment groups found that patients who received muscle relaxants had a 2.00 (95% CI: 1.14-3.49) times higher risk of delirium compared with controls ( P=0.015 )., Conclusion: Postoperative use of muscle relaxants as part of a multimodal analgesia regimen was associated with an increased risk of delirium in older adults after lumber fusion surgery. Although muscle relaxants may be beneficial in select patients, they should be used with caution in individuals at high risk for postoperative delirium., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Intrathecal baclofen (ITB) therapy effectively treats spasticity caused by brain or spinal cord lesions. However, only a few studies compare the course of treatment for different diseases. We investigated the change in daily dose of baclofen per year and its associated adverse events in patients presenting with the three most common etiologies at our institute: hereditary spastic paraplegia, cerebral palsy, and spinal cord injury. The ITB pumps were implanted from July 2007 to August 2019, with a mean follow-up period of 70 months. In patients with hereditary spastic paraplegia, baclofen dosage was reduced after eight years following ITB introduction, and the treatment was terminated in one patient owing to disease progression. In patients with cerebral palsy, the dosage increased gradually, and became constant in the 11th year. Patients with spinal cord injury gradually increased their baclofen dosage throughout the entire observation period. Severity and adverse event rates were higher in patients with cerebral palsy than in others. The degree and progression of spasticity varied depending on the causative disease. Understanding the characteristics and natural history of each disease is important when continuing ITB treatment.

Competing Interests: Competing interests: None declared.

Background: Baclofen is widely used for spastic disorders and, most recently, for addictive disorders. The first signals of baclofen abuse occurred in the last decade. This study aims to assess the motives, diversion sources, and routes of administration associated with the non-medical use of baclofen and examine health problems related to the non-medical use of baclofen., Methods: Spontaneous reports of baclofen abuse reported to the addictovigilance centre of East France were analysed. A literature search was conducted using PubMed®, Web of Sciences®, and Google Scholar® databases. Both investigations were performed in February 2021 without a time limit., Results: Forty-six cases were analysed (33 from the literature review and 13 from the addictovigilance base). Baclofen's non-medical use mainly affected male subjects with addictive history, but issues of primary abuse in subjects without any substance abuse history were also observed. Euphoria search was the most common reason for misuse. The route of administration included oral, snorting, and sublingual use. Some cases involving illegal sources were also observed. Most patients misusing baclofen presented severe complications, mainly represented by neurological and respiratory disturbances. Physical and psychological dependence on baclofen was observed in three persons., Conclusions: Although baclofen abuse remains relatively infrequent or (most likely) underestimated, this study helped confirm baclofen's intrinsic abuse potential and make visible the baclofen-abuse-related health visible harms. Careful consideration and benefit-risk analysis should be employed when prescribing baclofen, and emergency departments should be aware of baclofen dangers in abuse situations., (Copyright © 2023 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

Background: Long-term use of antipsychotics or other dopamine antagonists can result in the extrapyramidal side effect of tardive dyskinesia (TD).Case presentation: An 18-year-old female patient experienced abnormal speech and behavior and because of an equivocal diagnosis, she was given daily doses of 300 mg of quetiapine and 60 mg of ziprasidone. She had used these medications for 2 years before the appearance of involuntary abnormal movements. These movements, which were classified as TD, steadily worsened and markedly interfered with her daily life. Following a trial-and-error course of therapy with vitamin E, vitamin B6, amantadine, valproic acid sodium, lorazepam, and diazepam, the drugs were gradually reduced and stopped, yet the aberrant movements persisted. Finally, the patient was given olanzapine, clonazepam, baclofen, and gabapentin. The Abnormal Involuntary Movement Scale was used to assess changes in the patient's condition. Her TD was efficiently managed through co-administration of olanzapine, clonazepam, baclofen, and gabapentin., Conclusions: The possibility of TD inducing by antipsychotic use is a clinical concern, even though atypical antipsychotics decrease the incidence of extrapyramidal side effects, and it cannot be entirely excluded. This report provides useful insights into the management of TD and will help clinicians manage similar cases., Competing Interests: Declaration of conflicting interestsThe authors declare that they have no competing interests.

Background: The activities related to intrathecal baclofen (ITB) therapy could not be interrupted at the outbreak of COVID-19 pandemic due to possible life-threatening related complications such as withdrawal and over dosage syndromes. In this study we reported the different adopted strategies to manage patients with an ITB implanted infusion pump during the pandemic period and studied the impact of these strategies on experiences reported from patients and their caregivers, assessed through a specific survey., Methods: Thirty-five patients (mean age: 43.71±12.33 years) were included. Their clinical and medical data were recorded and observed from March 2020 to March 2021 and different strategies implemented in order to limit patients and providers risk of exposure to COVID-19. The impact of these strategies was assessed trough a survey that was performed after the first two months of pandemic (coinciding with the period of general lockdown) and after one year from the pandemic onset., Results: We observed a statistically significant improvement of the following items: difficulties in reaching medical clinic (P=0.0072), continuation of physical therapy (P=0.0021) and feelings of anxiety in medical conditions (P=0.0006). Considering the difficulties in communications with the medical staff we obtained optimal scores both at the beginning of pandemic and after one year from the pandemic onset without significant difference., Conclusions: Our survey showed that the adopted strategies provided a feeling of confidence and safety among ITB patients and their caregivers during the COVID-19 pandemic. We think that a clear communication is always of paramount importance to manage these patients.

Baclofen may reduce the symptoms of alcohol withdrawal, as an alternative or as an adjuvant for benzodiazepines, but the available data are insufficient to support baclofen-assisted alcohol withdrawal. This study investigated the need for diazepam during acute alcohol withdrawal in patients receiving baclofen. In a single-blind, dose-dependent randomized controlled trial with three study arms, 63 patients with alcohol use disorder, starting in-patient benzodiazepine-assisted alcohol detoxification, were randomly assigned to receive placebo (n = 18), baclofen 30 mg/day (N = 20), or baclofen 60 mg/day (N = 25) for 7 days. Diazepam was provided as needed based on the withdrawal symptoms stated by Clinical Institute Withdrawal Assessment for Alcohol-revised. The primary outcome measure was the number of patients in need of diazepam during alcohol detoxification. Secondary outcome measure included the between-group difference in the amount of diazepam needed during alcohol detoxification. Using baclofen 60 mg/day, 32% of patients needed additional diazepam compared to 35% on baclofen 30 mg/day and compared to 72% on placebo (P = .013). The median total amount of diazepam needed was significantly lower in patients receiving baclofen 60 mg/day (0 ± 10 mg diazepam) and baclofen 30 mg/day (0 ± 10 mg diazepam) compared to placebo (10 ± 43 mg diazepam; P = .017). Adverse events were comparable between patients on baclofen and placebo. Baclofen can reduce the withdrawal symptoms during alcohol detoxification. Baclofen was well tolerated and may be considered for the management of alcohol withdrawal syndrome, especially useful in situations where benzodiazepines should be withheld, such as patients with liver impairment., (© The Author(s) 2023. Medical Council on Alcohol and Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Since the first implantation in July 2001, the intrathecal baclofen (ITB) therapy for patients with generalized spasticity has been used in Slovenia for 20 years. The aim of this retrospective study was to evaluate the rates of different complications, especially if catheter-related complications were less frequent after the introduction of the coated catheter type in February 2013, and the potential correlation between higher baclofen doses and the incidence of complications. We retrospectively collected data from all patients in the registry during the period from 3 July 2001 to 31 December 2021. Among 138 patients (48 females), 120 patients had the first ITB system implanted at the University Medical Centre Ljubljana. Forty-three complications were reported in 38 patients (27%), with a total complication rate of 0.203/1000 days or 0.074/pump year. The most frequent was catheter-related (0.083/1000 days or 0.030/pump year), followed by skin-related (0.063/1000 days or 0.023/pump year) and pump-related complication (0.026/1000 days or 0.009/pump year). The incidence of catheter-related complications decreased significantly since the use of Ascenda type catheter: 14/7 complications per 88/147 implantations ( P  = 0.008). Patients with complications had a statistically significantly higher dose of baclofen: median 400 µg/24h vs. median 300 µg/24h ( P  = 0.016). Our retrospective analysis confirmed a significant decrease of catheter-related complications after the implementation of Ascenda type catheter in February 2013. Patients with a higher ITB dose had a statistically significantly higher incidence of complications. The total complication rate was a bit higher as previously reported in other studies, which is consistent with a long follow-up time., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Baclofen is the only drug that has been investigated in randomized controlled studies for anti-craving in patients with alcohol use disorder (AUD) and liver disease. However, the results of its efficacy are controversial due to limited case numbers; therefore, a meta-analysis of all available studies is needed to verify efficacy and safety in this population. This systematic review and meta-analysis were conducted according to the Cochrane Collaboration Handbook (PROSPERO ID: CRD42021284439) clauses. PubMed, Embase, Medline, Cochrane, and Clinical Trials. Gov were searched for patients with AUD co-morbid liver diseases who used baclofen to maintain abstinence. The primary outcome was maintaining abstinence. Baclofen safety was evaluated by adverse reaction occurrence during treatment. A total of 322 patients with AUD co-morbid liver diseases (alcohol-related liver disease, hepatitis C, or cirrhosis) from five studies were included. The total abstinence rate was 53% (95% CI: 0.23-0.84). Specifically, the abstinence rate in patients with alcohol-related liver disease and cirrhosis was 63% and 55%, respectively. We further analyzed the two included randomized controlled studies to compare the efficacy between baclofen and a placebo. There was no significant difference in abstinence rates between baclofen and the placebo (RR: 1.42, 95% CI: 0.41-4.92). One serious adverse event was reported, and no cases of baclofen addiction were found. The abstinence rate in patients with AUD co-morbid liver diseases was 53%; however, the efficacy of baclofen for maintaining abstinence in this population still needs to be validated with further studies., Competing Interests: Declaration of competing interest All authors declare no conflict of interest of this work., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Baclofen and tizanidine are both muscle relaxants that carry the risk for neuropsychiatric events in older adults but there is a lack of data directly comparing their safety. This study aimed to investigate the relative risk between these two medications in causing injury and delirium in older adults., Methods: This was a retrospective cohort study that was completed in an integrated healthcare system in the United States and included patients aged 65 years or older who started baclofen or tizanidine for the treatment of musculoskeletal pain from January 2016 through December 2018. Outcomes included new incidence of injury (concussion, contusion, dislocation, fall, fracture, or other injuries) and delirium. The cohort was followed from the initiation of therapy until the first occurrence of any of the following events: end of the index drug exposure, end of health plan membership, death, or the study end date of December 31st, 2019. Descriptive statistics were used to compare baseline patient characteristics between baclofen and tizanidine treatment groups. Cox proportional hazards model was used to calculate adjusted hazard ratios (HRs) with 95% confidence intervals., Results: The final study cohort included 12,101 and 6,027 older adults in the baclofen and tizanidine group respectively (mean age 72.2 ± 6.2 years old, 59% female). Older adults newly started on baclofen had a greater risk of injury (HR = 1.54, 95% CI = 1.21-1.96, P = < 0.001) and delirium (HR = 3.33, 95% CI = 2.11-5.26, p = <0.001) compared to those started on tizanidine., Conclusion: The results of this study suggest that baclofen is associated with higher incidences of injury and delirium compared to tizanidine when used for the treatment of musculoskeletal pain. Future studies should investigate if these risks are dose-related and include a comparison group not exposed to either drug., (© 2023 The American Geriatrics Society.)

Background: Intrathecal baclofen therapy can substantially improve symptoms in most patients with severe spasticity due to traumatic spinal cord injury, multiple sclerosis, or cerebral paresis. To the best of our knowledge, decompression surgeries at the intrathecal catheter insertion site in patients with a preexisting intrathecal pump for drug delivery have not been reported., Case Presentation: We report the case of a 61-year-old Japanese man with lumbar spinal stenosis who underwent intrathecal baclofen therapy. We performed decompression for lumbar spinal stenosis at the intrathecal catheter insertion site during intrathecal baclofen therapy. The yellow ligament was removed by partial resection of the lamina under a microscope to avoid damage to the intrathecal catheter. The dura mater was distended. No obvious cerebrospinal fluid leakage was observed. Postoperatively, lumbar spinal stenosis symptoms improved, and spasticity remained well controlled with intrathecal baclofen therapy., Conclusions: This is the first reported case of lumbar spinal stenosis decompression at an intrathecal catheter insertion site during intrathecal baclofen therapy. Preoperative preparation is necessary, as the intrathecal catheter may be replaced during surgery. We performed surgery without removing or replacing the intrathecal catheter, taking care not to damage the spinal cord by migrating the intrathecal catheter., (© 2023. The Author(s).)

Background: Baclofen can decrease rumination frequency in adults with rumination syndrome. Outcomes of baclofen treatment in children with rumination syndrome have not been described. The aim of this study was to examine the safety and efficacy of baclofen in children with rumination syndrome in combination with behavioral therapy at a single center., Methods: We performed a retrospective review of children aged 0-18 years with rumination syndrome based on Rome criteria and prescribed baclofen by a pediatric gastroenterologist at the Nationwide Children's Hospital, Columbus, Ohio, USA, between 2012 and 2019. Children without follow-up data or who were prescribed baclofen for other symptoms were excluded., Results: We identified 44 children with rumination syndrome who were prescribed baclofen by a pediatric gastroenterologist. Seventeen either did not have follow-up data or never started the medication. We included 27 patients in the study: 22 (81.5%) female, median age 14.5 years (range 10-18 years) and 100% Caucasian. Twenty patients (74%) received baclofen 5 mg and seven patients (26%) received baclofen 10 mg three times daily. Most patients received behavioral therapy and baclofen simultaneously. Thirteen patients (48%) reported improvement in symptoms, primarily a decrease in rumination frequency, at their first follow-up visit. Regurgitation frequency per week decreased after starting baclofen (p < 0.05). One patient experienced dizziness. No other side effects were reported., Conclusion: Nearly half of our patients with rumination syndrome improved after baclofen. It was well tolerated with minimal side effects. This suggests that baclofen in addition to behavioral therapy can improve symptoms of rumination syndrome. Prospective, controlled studies in a larger cohort of children with rumination syndrome are needed to confirm these findings., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: To quantify the risk of encephalopathy associated with oral baclofen compared with other muscle relaxants-tizanidine or cyclobenzaprine., Patients and Methods: We conducted a new-user, active-comparator study of 2 pairwise cohorts using tertiary health system data from Geisinger Health in Pennsylvania (January 1, 2005, through December 31, 2018). Adults (aged ≥18 years) newly treated with baclofen or tizanidine were included in cohort 1. Adults newly treated with baclofen or cyclobenzaprine were included in cohort 2. Propensity score-based inverse probability of treatment weighting (IPTW) was used to balance the respective cohorts on 45 patient characteristics. Fine-Gray competing risk regression was used to estimate the risk of encephalopathy., Results: Cohort 1 included 16,192 new baclofen users and 9782 new tizanidine users. The 30-day risk of encephalopathy was higher in patients treated with baclofen vs tizanidine (IPTW incidence rate, 64.7 vs 28.3 per 1000 person-years) with an IPTW subdistribution hazard ratio (SHR) of 2.29 (95% CI, 1.43 to 3.67). This risk persisted through 1 year (SHR, 1.32 [95% CI, 1.07 to 1.64]). Similarly in cohort 2, baclofen vs cyclobenzaprine was associated with a greater risk of encephalopathy at 30 days (SHR, 2.35 [95% CI, 1.59 to 3.48]) that persisted through the first year of treatment (SHR, 1.94 [95% CI, 1.56 to 2.40])., Conclusion: The risk of encephalopathy was greater with baclofen vs tizanidine or cyclobenzaprine use. The elevated risk was apparent as early as 30 days and persisted through the first year of treatment. Our findings from routine care settings may inform shared treatment decisions between patients and prescribers., (Copyright © 2022 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Introduction: Intrathecal Baclofen (ITB) is used for the treatment of spasticity. Pump complications are most commonly related to surgical implantation or catheter dysfunction. Less common complications include catheter access port dysfunction, motor failure from excessive wear on motor gear shafts, or a complete stall of the motor., Case Presentation: 37-year-old with T9 motor complete paraplegia with ITB presented in baclofen withdrawal. Workup revealed that the pump's motor was not turning, requiring pump replacement. Questioning revealed that he had not undergone any MRI studies within the past six months, but that he recently purchased a new iPhone. The phone was 2-3 inches away from the pump for up to twelve hours a day, carried in a fanny pack around his waist., Discussion: We present a case of motor pump failure from long term exposure to a magnetic field from a new iPhone. The ability of iPhones to overpower an ITB pump magnet is not widely known. In 2021, the Food and Drug Administration published a report regarding the effects of magnets in consumer electronics on implanted medical devices, recommending that such electronics should be kept at least 6 inches from the device. Providers should be aware of the ability of new models of commonly used electronic devices to stall the ITB motor to avoid life-threatening complications of baclofen withdrawal., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: Phenibut is a widely available gamma-aminobutyric acid B receptor agonist. When taken chronically, phenibut causes dependence and subsequent withdrawal if stopped. Baclofen, a gamma-aminobutyric acid B receptor agonist structurally related to phenibut, has been used to manage phenibut withdrawal (PW), although baclofen doses for PW are not well defined and may exceed Food and Drug Administration-approved doses. Little data described outcomes from baclofen use., Methods: This case details a patient who experienced a seizure while on baclofen 10 mg thrice daily as monotherapy for PW and highlights a potential risk of underdosing baclofen as monotherapy in the management of PW., Results: A man in his early 30s with anxiety, depression, and substance use disorder presented to the emergency department by family for lethargy and confusion starting earlier that day. He had been using 25-30 g of phenibut daily for the past 6 months. On arrival, he was hypertensive, tachycardic, tachypneic, and lethargic. The patient received 1 mg of intravenous lorazepam and was admitted to the hospital for presumed PW. His symptoms improved overnight, and he was discharged on 10 mg of baclofen thrice daily. He returned 28 hours later after having a seizure and required intensive care admission in addition to multimodal drug therapy., Conclusions: Phenibut use is rising, and treatment options for PW, such as baclofen, warrant additional study. Potential risks of underdosing baclofen if used as monotherapy in PW may include seizures as withdrawal progresses. Baclofen's role in therapy may be more appropriate as an adjunct than a cornerstone of therapy. Treatment done in consultation with providers experienced in managing withdrawal such as a toxicologist may help reduce this risk., Competing Interests: Conflicts of Interest and Source of Funding: The authors have no conflicts of interest to declare., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To systematically review case reports of psychosis related to withdrawal or overdose of baclofen, which is a gamma-aminobutyric acid (GABA) B agonist., Methods: PubMed, MEDLINE, CINAHL, and PsychINFO were searched to identify articles related to psychosis secondary to withdrawal or overdose of baclofen using the terms 'baclofen' and ' psychosis'. Comparisons were made between cases in terms of concomitant antipsychotic use, diagnosis of delirium, and evidence of association. Quality of case reports was assessed using the CARE Case Report Guidelines checklist., Results: In total, 34 patients from 28 case reports were reviewed. Twenty-three patients experienced psychosis upon baclofen withdrawal; among them, 18 had resolution of psychosis upon reinitiation of baclofen, whereas antipsychotic monotherapy was less successful (only four of eight patients responded). An additional baclofen withdrawal period led to recurrence of psychotic symptoms in four of seven patients. Eleven patients had psychosis on induction or after overdose of baclofen; among them, four patients had resolution of psychosis upon cessation of baclofen. The mean quality of the case reports was 6.4 of 13., Conclusion: Considering its GABAergic agonism, along with evidence of psychosis on induction or withdrawal, baclofen may have some antipsychotic and pro-psychotic properties., Competing Interests: As the editor of the journal, SKWC was not involved in the peer review process. Other authors have disclosed no conflicts of interest.

Objective: To investigate patients' expectations, met/unmet expectations and satisfaction with intrathecal baclofen treatment in relation to effect on spasticity, pain intensity, sleep quality, occupational performance, well-being and self-efficacy., Design: A prospective longitudinal study with follow-up at 1 year., Patients: Consecutive patients, age ≥ 18 years with a disabling spasticity of cerebral or spinal origin selected for intrathecal baclofen treatment at 2 university hospitals in Sweden were included. From August 2016 to June 2019, 35 patients began intrathecal baclofen treatment; 29 patients were included and completed the study., Methods: Baseline and 1-year follow-up included assessment of spasticity by physiotherapists, a semi-structured interview regarding occupational performance using the Canadian Occupational Performance Measure and a questionnaire., Results: Overall satisfaction with treatment and satisfaction with occupational performance were reported as moderate. Important variables that explained satisfaction with occupational performance were improvements in performance, expectations and performance before treatment. Patients had higher expectations compared with the 1-year outcomes regarding occupational performance, spasticity, pain intensity and sleep quality, although improvements were reported., Conclusion: A thorough discussion of goal setting with intrathecal baclofen treatment before implantation is necessary to give patients individual and realistic expectations.

Background: Alcohol use disorder (AUD) is one of the most widespread psychiatric disorders leading to detrimental consequences to people with this disorder and others. Worldwide, the prevalence of heavy episodic drinking (30-day prevalence of at least one occasion of 60 g of pure alcohol intake among current drinkers) is estimated at 20% and the prevalence of AUD at 5% of the adult general population, with highest prevalence in Europe and North America. Therapeutic approaches, including pharmacotherapy, play an important role in treating people with AUD. This is an update of a Cochrane Review first published in 2018., Objectives: To evaluate the benefits and harms of baclofen on achieving and maintaining abstinence or reducing alcohol consumption in people with AUD compared to placebo, no treatment or any other pharmacological relapse prevention treatment., Search Methods: We used standard, extensive Cochrane search methods. The latest search was 22 November 2021., Selection Criteria: Randomised controlled trials (RCTs) of at least four weeks' treatment duration and 12 weeks' overall study duration comparing baclofen for AUD treatment with placebo, no treatment or other treatments., Data Collection and Analysis: We used standard Cochrane methods. Our primary outcomes were 1. relapse, 2. frequency of use, 3. amount of use, 4. adverse events, 5. dropouts from treatment and 6. dropouts from treatment due to adverse events. Our secondary outcomes were 7. craving, 8. anxiety, 9. depression and 10. frequency of most relevant adverse events., Main Results: We included 17 RCTs (1818 participants) with a diagnosis of alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition or International Classification of Diseases 10th edition criteria. Mean age was 46.5 years and 70% were men. Ten studies compared baclofen to placebo or another medication; seven compared two baclofen doses to placebo or another medication. Globally, 15 studies compared baclofen to placebo, two baclofen to acamprosate and two baclofen to naltrexone. In 16 studies, participants received psychosocial treatments. We judged most studies at low risk of selection, performance, detection (subjective outcome), attrition and reporting bias. Ten studies detoxified participants before treatment; in seven studies, participants were still drinking at the beginning of treatment. Treatment duration was 12 weeks for 15 RCTs and longer in two studies. Baclofen daily dose was 30 mg to 300 mg: 10 RCTs used low doses (30 mg or less); eight RCTs medium doses (above 30 and 100 mg or less) and four RCTs high doses (above 100 mg). Compared to placebo, moderate-certainty evidence found that baclofen probably decreases the risk to relapse (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.77 to 0.99; 12 studies, 1057 participants). This result was confirmed among detoxified participants but not among other subgroups of participants. High-certainty evidence found that baclofen increases the percentage of days abstinent (mean difference (MD) 9.07, 95% CI 3.30 to 14.85; 16 studies, 1273 participants). This result was confirmed among all subgroups of participants except non-detoxified or those who received medium doses. There was no difference between baclofen and placebo in the other primary outcomes: heavy drinking days (standardised mean difference (SMD) -0.18, 95% CI -0.48 to 0.11; 13 studies, 840 participants; moderate-certainty evidence); number of drinks per drinking days (MD -0.45, 95% CI -1.20 to 0.30; 9 studies, 392 participants; moderate-certainty evidence); number of participants with at least one adverse event (RR 1.05, 95% CI 0.99 to 1.11; 10 studies, 738 participants; high-certainty evidence); dropouts (RR 0.88, 95% CI 0.74 to 1.03; 17 studies, 1563 participants; high-certainty evidence); dropouts due to adverse events (RR 1.39, 95% CI 0.89 to 2.18; 16 studies, 1499 participants; high-certainty evidence). These results were confirmed by subgroup analyses except than for the dropouts that resulted lower among participants who received high doses of baclofen and studies longer than 12 weeks. Compared to placebo, there was no difference in craving (SMD -0.16, 95% CI -0.37 to 0.04; 17 studies, 1275 participants), anxiety (MD -0.01, 95% CI -0.14 to 0.11; 15 studies, 1123 participants) and depression (SMD 0.07, 95% CI -0.12 to 0.27; 11 studies, 1029 participants). Concerning the specific adverse events, baclofen increases fatigue, dizziness, somnolence/sedation, dry mouth, paraesthesia and muscle spasms/rigidity. There was no difference in the other adverse events. Compared to acamprosate, one study (60 participants) found no differences in any outcomes but the evidence was very uncertain: relapse (RR 1.25, 95% CI 0.71 to 2.20; very low-certainty evidence); number of participants with at least one adverse event (RR 0.63, 95% CI 0.23 to 1.69; very low-certainty evidence); dropouts (RR 0.56, 95% CI 0.21 to 1.46; very low-certainty evidence); dropouts due to adverse events (RR 0.33, 95% CI 0.01 to 7.87; very low-certainty evidence) and craving (MD 5.80, 95% CI -11.84 to 23.44); and all the adverse events evaluated. Compared to naltrexone, baclofen may increase the risk of relapse (RR 2.50, 95% CI 1.12 to 5.56; 1 study, 60 participants; very low-certainty evidence) and decrease the number of participants with at least one adverse event (RR 0.35, 95% CI 0.15 to 0.80; 2 studies, 80 participants; very low-certainty evidence) but the evidence is very uncertain. One study (60 participants) found no difference between baclofen and naltrexone in the dropouts at the end of treatment (RR 1.00, 95% CI 0.32 to 3.10; very low-certainty evidence), craving (MD 2.08, 95% CI -3.71 to 7.87), and all the adverse events evaluated., Authors' Conclusions: Baclofen likely reduces the risk of relapse to any drinking and increases the percentage of abstinent days, mainly among detoxified participants. It does not increase the number of participants with at least one adverse event, those who dropout for any reason or due to adverse events. It probably does not reduce number of heavy drinking days and the number of drinks per drinking days. Current evidence suggests that baclofen may help people with AUD in maintaining abstinence. The results of comparisons of baclofen with acamprosate and naltrexone were mainly based on only one study., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Baclofen is a β-(p-chlorophenyl) derivative of the neurotransmitter y-aminobutyrio acid (GABA). This centrally-acting GABA agonist is prescribed as therapy for spasticity in the spinal cord region. The drug is predominantly excreted by the kidney, thus making patients with kidney disease susceptible to side effects. We report on a patient with end-stage renal disease who developed baclofen toxicity, which was successfully treated with intense hemodialysis., (Copyright © 2023 Copyright: © 2023 Saudi Journal of Kidney Diseases and Transplantation.)

Background: We aimed to determine medications' comparative efficacy and safety for adults with alcohol use disorders., Methods: We searched eleven electronic data sources for randomized clinical trials with at least 4 weeks of treatment reporting on alcohol consumption (total abstinence and reduced heavy drinking), dropouts, and dropouts due to adverse events. We conducted network meta-analyses using random-effects, frequentist models, and calculated summary rate ratios (RRs) with 95% confidence intervals (CIs)., Results: We included 156 trials (N = 27,334). Nefazodone (RR = 2.11; 95% CI, 1.42-3.13), aripiprazole (RR = 1.97; 95% CI, 1.36-2.88), carbamazepine (RR = 1.85; 95% CI, 1.03-3.32), and nalmefene (RR = 1.17; 95% CI, 1.01-1.35) were associated with the most dropouts. Baclofen (RR = 0.83; 95% CI, 0.70-0.97) and pregabalin (RR = 0.63; 95% CI, 0.43-0.94) caused fewer dropouts than placebo. Nalmefene (RR = 3.26; 95% CI, 2.34-4.55), fluvoxamine (RR = 3.08; 95% CI, 1.59-5.94), and topiramate (RR=2.18; 95% CI, 1.36-3.51) caused more dropouts from adverse events over placebo. Gamma-hydroxy-butyrate (RR = 1.90; 95% CI, 1.03-3.53), baclofen (RR = 1.80; 95% CI, 1.39-2.34), disulfiram (RR = 1.71; 95% CI, 1.39-2.10), gabapentin (RR = 1.66; 95% CI, 1.04-2.67), acamprosate (RR = 1.33; 95% CI, 1.15-1.54), and oral naltrexone (RR = 1.15; 95% CI, 1.01-1.32) improved total abstinence over placebo (Fig. 3C). For reduced heavy drinking, disulfiram (RR = 0.19; 95% CI, 0.10-0.35), baclofen (RR = 0.72; 95% CI, 0.57-0.91), acamprosate (RR = 0.78; 95% CI, 0.70-0.86), and oral naltrexone (RR = 0.81; 95% CI, 0.73-0.90) were efficacious against placebo., Conclusions: The current meta-analyses provide evidence that several medications for AUDs are effective and safe and encourage the expanded use of these medications in the clinical setting. Our review found that acamprosate (2-3 g/d), disulfiram (250-500 mg/d), baclofen (30 mg/d), and oral naltrexone (50 mg/d) had the best evidence for improving abstinence and heavy drinking for patients with AUD., Prospero: CRD42020208946., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 American Society of Addiction Medicine.)

Background: Treatment of opiate addiction with opiate substitution treatment (e.g. methadone) is beneficial. However, some individuals desire or would benefit from abstinence but there are limited options to attenuate problems with opiate withdrawal. Preclinical and preliminary clinical evidence suggests that the GABA-B agonist, baclofen, has the desired properties to facilitate opiate detoxification and prevent relapse. This study aims to understand whether there are any safety issues in administering baclofen to opioid-dependent individuals receiving methadone., Methods: Opiate-dependent individuals (DSM-5 severe opioid use disorder) maintained on methadone will be recruited from addiction services in northwest London (NHS and third sector providers). Participants will be medically healthy with no severe chronic obstructive pulmonary disease or type 2 respiratory failure, no current dependence on other substances (excluding nicotine), no current severe DSM-5 psychiatric disorders, and no contraindications for baclofen or 4800 IU vitamin D (placebo). Eligible participants will be randomised in a 3:1 ratio to receive baclofen or placebo in an adaptive, single-blind, ascending dose design. A Bayesian dose-escalation model will inform the baclofen dose (10, 30, 60, or 90 mg) based on the incidence of 'dose-limiting toxicity' (DLT) events and participant-specific methadone dose. A range of respiratory, cardiovascular, and sedative measures including the National Early Warning Score (NEWS2) and Glasgow Coma Scale will determine DLT. On the experimental day, participants will consume their usual daily dose of methadone followed by an acute dose of baclofen or placebo (vitamin D3) ~ 1 h later. Measures including oxygen saturation, transcutaneous CO 2 , respiratory rate, QTc interval, subjective effects (sedation, drug liking, craving), plasma levels (baclofen, methadone), and adverse events will be obtained using validated questionnaires and examinations periodically for 5 h after dosing., Discussion: Study outcomes will determine what dose of baclofen is safe to prescribe to those receiving methadone, to inform a subsequent proof-of-concept trial of the efficacy baclofen to facilitate opiate detoxification. To proceed, the minimum acceptable dose is 30 mg of baclofen in patients receiving ≤ 60 mg/day methadone based on the clinical experience of baclofen's use in alcoholism and guidelines for the management of opiate dependence., Trial Registration: Clinicaltrials.gov NCT05161351. Registered on 16 December 2021., (© 2022. The Author(s).)

Introduction: Oral baclofen is commonly used for spasticity management, especially with neurogenic bladder in spinal cord injury (SCI). A less common side effect of baclofen is transient alterations of consciousness, which can easily be confused for altered mental status secondary to orthostatic hypotension in SCI., Case Presentation: A 43-year-old man with an acute SCI secondary to an aortic dissection was found to have episodes of confusion after titrating oral baclofen from 5 mg three times per day to 10 mg three times per day at an acute rehabilitation facility. Orthostatic hypotension was initially suspected as the cause of transient alterations of consciousness; however, he was never found to be hypotensive during these episodes. His confusion resolved several days after discontinuation of baclofen., Discussion: Although, confusion and lightheadedness in SCI are commonly caused by orthostatic hypotension, it is important for physicians to be cognizant of baclofen's side effects, which increase in the setting of acute kidney injury (AKI). If an adverse effect is suspected, baclofen should be tapered while remaining observant for signs of baclofen withdrawal, which can be life-threatening. This case report is a reminder for clinicians to be aware of the uncommon adverse effects of baclofen when initiating therapy in SCI, especially in patients with AKI and neurogenic bladders., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Background: The intrathecal baclofen (ITB) pump is an effective treatment for patients with spasticity unresponsive to oral medication., Case Report: A 31-year-old woman with spinal cord injury sequelae was admitted to the emergency department due to sudden headache and excessive confusion. The patient was on ITB for lower limb spasticity. On presentation, her vital signs revealed blood pressure of 171/106 mm Hg, heart rate of 141 beats/min, and temperature of 39.0°C. Antibiotics were promptly administered intravenously for suspicion of bacterial meningitis. Based on magnetic resonance imaging and cerebrospinal fluid findings, as well as clinical signs such as marked lower limb spasticity, the final diagnosis was determined to be baclofen withdrawal syndrome complicated by reversible posterior leukoencephalopathy syndrome (RPLS). Improved consciousness was quickly achieved on blood pressure control. Resolution of spasticity was achieved after intravenous midazolam and intrathecal baclofen via lumbar puncture. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Baclofen withdrawal syndrome is the leading differential diagnosis for impaired consciousness and fever among patients using ITB pumps. Moreover, baclofen withdrawal syndrome mimics a wide variety of conditions, including sepsis. This unique case was complicated by intrathecal baclofen withdrawal syndrome coexisting with RPLS, thus presenting more similarly to bacterial meningitis than the usual baclofen withdrawal, due to marked headache, altered consciousness, and generalized convulsive symptoms. In addition to general withdrawal management, commencement of antihypertensive therapy for RPLS may have an immediate effect on the improvement of impaired consciousness., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: Patients with alcohol use disorder (AUD) and liver cirrhosis benefit from stopping alcohol intake. Baclofen has been trialled for AUD in cirrhosis and appears to be effective. However, in patients without cirrhosis acamprosate is safer and more efficacious. Acamprosate is rarely used in cirrhosis due to safety concerns: the only published report was for 24 h in a controlled setting. Our centre uses both medications off-label in cirrhotic patients. We performed an audit to pragmatically compare the safety of acamprosate to baclofen in these patients., Methods: The electronic records of patients prescribed acamprosate or baclofen between 01/04/17 and 31/03/20 were retrospectively reviewed. Adverse events and abstinence at last follow-up were compared by Student's t-test, Mann-Whitney U or chi-square test. Confounding variables were evaluated by logistic regression., Results: In total 48 cirrhotic patients taking acamprosate (median 84 days, range 2-524); 44 baclofen (247 days, 8-910) met inclusion criteria. At baseline, 41% had Childs-Pugh B or C cirrhosis. More patients taking baclofen had an unplanned hospital admission or attendance (23 vs 13; P = 0.013) and the mean number per patient was higher (1.6 vs 0.6; P = 0.032). Sub-group analysis revealed increased admissions in actively drinking patients prescribed baclofen to achieve abstinence (mean 2.4 vs 0.6; P = 0.020); acamprosate use was associated with a reduced chance of admission or attendance (OR, 0.284; 0.095-0.854; P = 0.025) independent of treatment length. No difference in efficacy was observed., Conclusions: In patients with cirrhosis, acamprosate was associated with fewer unplanned admissions than baclofen, hence may be safer despite historical concerns., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

It is known that phoenixin-14 (PNX-14) has a mediatory role in reproduction; however, there is no report on the role of the PNX-14 on epilepsy. Therefore, this study aimed to investigate the antiepileptic effects of the PNX-14 on the pentylenetetrazol (PTZ)-induced epilepsy in the stages of the estrous cycle among rats. A total of 168 adult female Wistar rats were randomly divided into seven groups, including control (intracerebroventricular injection was performed with saline), PNX-14 (5 µg), PNX-14 (10 µg), bicuculline (competitive antagonist of GABA A receptors; 5 nmol)+PNX-14 (5 µg), bicuculline (BIC) (5 nmol)+PNX-14 (10 µg), saclofen (competitive antagonist of GABA B receptors; 2.5 µg)+PNX-14 (5 µg), and saclofen (2.5 µg)+PNX-14 (10 µg) in proestrus, estrus, metestrus, and diestrus. Afterward, the control and treatment groups were followed by intraperitoneal administration of 80 mg/kg PTZ. Initiation time of myoclonic seizures (ITMS), initiation time of tonic-clonic seizures (ITTS), seizure duration (SD), and mortality rate (MR) were monitored and recorded for 30 min. According to the results, PNX-14 alone significantly reduced the SD and seizure mortality in all phases of estrus ( P <0.05). The injection of PNX-14 with BIC significantly reduced SD and seizure mortality in all estrus phases ( P <0.05). PNX-14 alone increased both ITMS and ITTS in all phases of estrus ( P <0.05). Furthermore, the injection of PNX-14 with BIC significantly reduced the effects of the PNX-14 on ITMS and ITTS in all estrus stages ( P <0.05). These results showed that the antiepileptic activity of PNX-14 was probably mediated by GABA A receptors, and this effect was more prominent during the luteal phase than the follicular phase., Competing Interests: The authors declare that they have no conflict of interest.

A woman in her 40s with advanced bladder cancer was admitted to hospital with hypercalcaemia of malignancy. Initially, she presented with non-specific symptoms of malaise, fatigue and general deterioration. She was treated with intravenous fluids and zoledronic acid in order to bring her calcium levels down, but subsequently developed significant hypocalcaemia. This manifested as tetany in the hands in the form of bilateral carpopedal spasm. She also reported perioral paraesthesia. Bloods during her admission revealed deranged electrolytes, and her vitamin D level was on the lower scale of normal (25 nmol/L). The patient's symptoms improved with electrolyte replacement and oral baclofen for her symptomatically distressing wrist and hand muscle spasms. This case report is a reminder that bisphosphonates can cause significant hypocalcaemia with symptoms of tetany, even when they are given for initial hypercalcaemia. Baclofen worked well to improve symptoms., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Complications of intrathecal baclofen treatment (ITB) with an implanted pump can be severe and require surgery. Surgical implantation techniques and catheter materials for continuous ITB treatment have improved over the past years with the aim to reduce complications., Objective: To assess: 1) the type and rate of complications of ITB that require surgical intervention, 2) which risk factors influence the occurrence of complications, and, specifically, 3) whether complication rate is influenced by type of catheter used., Methods: A retrospective cohort study was conducted including all children (<18 years old) in one university medical center with pump implantation between 2001 and 2017. All complications requiring surgery were recorded. Risk factors for surgical intervention were determined using multiple logistic regression analysis. Catheter related complications between two types of catheters (silicone vs coated) were compared., Results: In total, 88 complications of ITB treatment requiring surgery were found in 47 (36.2%) out of 130 children. These included catheter-related complications (55.7% of all complications), infections (21.6%), cerebrospinal fluid leakage (14.8%), and pump-related complications (7.9%). The silicone catheter type, used until 2012, was found to be a significant risk factor for complications (Odds Ratio 3.75; 95% CI: 1.30-10.83). Since the introduction of the coated catheter type, in 2012, the rate of catheter-related complications decreased, from 0.15 to 0.10 complications per pump year., Conclusion: The rate of surgical complications of intrathecal baclofen in children is high, and most frequently catheter-related. The number of complications decreased since the introduction of a new, coated, catheter in 2012. This study helps to inform children and their caregivers about the risk of possible complications of ITB, and to identify directions for future improvement of ITB care., (© 2022 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.)

Background: A severe baclofen intoxication is a potentially life-threatening condition. It is associated with coma and can cause brainstem reflexes to disappear, simulating a brain death-like condition. When given intensive supportive care and time, patients can recover without residual neurological damage., Case Report: We present a case of a patient with known spastic cerebral palsy who was found unresponsive with no signs of breathing. He was brought to the Emergency Department, intubated, put on the ventilator, and hemodynamically stabilized. Brainstem reflexes were absent and he appeared brain dead. During the secondary survey, an intrathecal baclofen pump was found at his left lower abdomen, with a swelling next to it. A baclofen intoxication was suspected. He was admitted to the Intensive Care Unit, and after 72 h of supportive care complete neurological recovery was achieved. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Systemic baclofen intoxication can simulate a brain death-like condition. There is no reliable correlation between baclofen serum levels and central nervous system depression in case of an intoxication. It is important for emergency physicians to recognize a baclofen intoxication as a possible cause of coma and absent brainstem reflexes. Recuperation is spontaneous and can follow within days without residual damage. Because these patients may be brought in after a period of apnea or cardiopulmonary resuscitation, focus may be on post-hypoxic encephalopathy considerations instead of a possible baclofen intoxication., (Copyright © 2021. Published by Elsevier Inc.)

The purpose of this study was to investigate the incidence of complications in pediatric spastic cerebral palsy (CP) patients weighing less than 20 kg at the time of intrathecal baclofen (ITB) pump implantation and to compare it with spastic CP patients heavier than 20 kg. Twenty-seven patients with spastic CP (14 males) treated with ITB implantation at our institution between January 2002 and January 2018 were retrospectively reviewed. Eight of the 27 patients had a bodyweight below 20 kg (group A) and 19 had weight above 20 kg (group B). Group A had a significantly more important proportion of patients with the Gross Motor Function Classification System V compared to group B (88 vs. 42%). The median follow-up was respectively 2.5 (1.8-4.6) and 4.6 (1.9-10.0) years in groups A and B. Median age at the time of ITB implantation was 7.4 (2.8-12.8) and 13.7 (6.5-16.8) years in groups A and B (P = 0.002). The proportion of patients with complications or reoperation was NS between groups A and B (P > 0.05). No postoperative infections were recorded in any of the groups. During follow-up, five patients died (63%) in group A and three (16%) in group B (P = 0.049) within 3.8 years on average after ITB implantation. ITB therapy in spastic CP patients weighing less than 20 kg seems to be as well tolerated and effective as it is in heavier (>20 kg) pediatric patients., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)