Doses Of Baclofen Research Articles

Challenges of patients with intrathecal baclofen pump therapy during COVID-19 pandemic in Saudi Arabia

Background: This study was carried out to analyze the effects of the COVID-19 pandemic on patients with intrathecal baclofen (ITB) therapy. Methods: Patients who came for ITB refill during the COVID-19 pandemic between March 2020 and August 2020 were contacted, and a survey was conducted regarding challenges faced during the COVID-19 pandemic. Data obtained from the chart review included demographics, diagnoses, pump information, baclofen dose, and COVID triage. Information was collected regarding travel arrangements, appointments, and problems related to ITB therapy or travel. The survey included 12 multiple-choice questions related to travel, appointment scheduling, and difficulties faced during the travel restrictions. Results: The study included 19 patients with ITB (mean age: 38.1±14.4) from outside Riyadh city who came for ITB refill during the COVID-19 pandemic. The majority of the patients were males. Spinal cord injury with paraplegia was the most common diagnosis (52.6%). In total, 7 patients had either clinical (31.6%) or travel-related difficulties (15.8%). No patient had ITB withdrawal at the time of the clinic visit. Nearly half (47.4%) of the patients had to change their appointment for refill. The percentage of patients who used a car as a mode of travel pre-COVID was 42.1%, which increased to 78.9% during the pandemic. They traveled 747.4±356.6 km (7.4±3.7 h) to reach the hospital for refill. Patients needed 1–4 accompanied persons for assistance during travel, with the majority (68.4%) requiring 2 accompanied persons. Statistical analysis did not reveal any significant associations between clinical or travel difficulties and appointment changes. Conclusions: A pandemic or similar disaster can pose challenges to patients on ITB therapy living in areas with limited access to specialized care. In this study, none of the patients had serious complications or adverse outcomes; however, the main difficulties were attributed to travel. It is crucial to establish strategies at institutional, regional, or national levels to formulate guidelines for managing patients with ITB therapy during a pandemic.

Postoperative outcomes and stimulation responses for sectioned nerve roots during selective dorsal rhizotomy in cerebral palsy

BackgroundCerebral palsy (CP) is the most cause of motor dysfunction in children. Selective dorsal rhizotomy (SDR) plays a major role in long term spasticity control. However, limited data exists on the effect of SDR on postoperative spasticity treatment requirements and supraspinal effects, and the stimulation responses of dorsal nerve roots in those with CP.MethodsThe current study included the outcome for 35 individuals undergoing SDR for motor functional outcome, spasticity, baclofen dose changes, botulinum toxin injection frequency, and spasticity related orthopedic procedures. We also report on the stimulation responses in 112 individuals who underwent SDR at our institution.ResultsThere was a significant difference in gross motor function measures (GMFM)-66 scores at last follow up that remained present when considering only ambulatory children but not with non-ambulatory children. Ashworth scores were significantly decreased for both upper and lower extremities after SDR at all follow up points. There was a significant decrease in Baclofen dose and botulinum toxin injections requirements after SDR, but no significant difference in the need for orthopedic intervention. A total of 5502 dorsal nerve roots were tested showing a decrease in stimulation intensity and increase in grade on the right side and for descending lumbosacral levels.ConclusionsSDR improves gross motor scores during short term follow up but has additional benefits in decreasing baclofen dosing and botulinum toxin injections requirements after surgery. They stimulation responses of sectioned dorsal nerve roots adds to the limited available data and our understanding of the pathological changes that occur in CP.

Use of Baclofen Premedication as an Analgesic Adjuvant in Patients Undergoing Percutaneous Nephrolithotripsy: A Placebo-Controlled, Double-Blind Randomized Trial.

Baclofen, a clinically available GABAB receptor agonist, produces nonopioid analgesia in multiple models of pain but has had limited studies related to perioperative pain control.The present study seeks to study effects of baclofen on postoperative pain measures and opioid use in adult patients subjected to percutaneous nephrolithotomy (PCNL). Using a placebo-controlled, double-blind methodology, a single 10 mg oral dose of baclofen or placebo was given prior to a surgery in 34 patients undergoing PCNL.Standardized intraoperative and postoperative protocols related to opioid use were followed.Use of postoperative opioids in the post-anesthesia care unitand for the first 24 hours following surgery were recorded as were pain scores and other medication use. There was a significant positive correlation in the use of postoperative opioids in patients who had a preceding history of opioid use.However, there were no significant differences in opioid use which could be attributed to baclofen.There were also no differences in postoperative vital signs, side effects or other medication use. Analgesic benefits of preoperative baclofen were not observed at the dose employed.Safety of the drug was observed.

Low-Dose Baclofen-Induced Encephalopathy in a Patient with End-Stage Renal Disease: A Case Report

Baclofen, a gamma-aminobutyric acid-B receptor agonist, is commonly used for central-origin muscle spasticity and spasm and neuropathic pain. Baclofen toxicity has been reported to cause a range of symptoms including drowsiness, confusion, respiratory depression, seizures, and even coma, particularly with dosage significantly exceeding therapeutic levels. Given that the baclofen is predominantly eliminated through the kidneys, patients with renal failure are at substantial risk for neurotoxic effects. We report a case of baclofen-induced encephalopathy in a patient with end-stage renal disease, characterized by an altered mental state with myoclonus following the consumption of a low dose of baclofen.

Nonselective lumbosacral ventral-dorsal rhizotomy for the management of lower-limb hypertonia in nonambulatory children with cerebral palsy.

Children with cerebral palsy (CP) often experience medically refractory hypertonia, for which there are surgical therapies including neuromodulation and rhizotomy. Traditional surgical treatment for medically refractory mixed hypertonia or dystonia includes intrathecal baclofen pumps and selective dorsal rhizotomy. A nonselective lumbosacral ventral-dorsal rhizotomy (VDR; ventral and dorsal roots lesioned by 80%-90%) has the potential to address the limitations of traditional surgical options. The authors highlighted the institutional safety and efficacy of nonselective lumbosacral VDR for palliative tone management in nonambulatory patients with more severe CP. The authors performed a retrospective analysis of patients who had undergone lumbosacral VDR between 2022 and 2023. Demographic factors, clinical variables, and operative characteristics were collected. The primary outcomes of interest included tone control and quality of life improvement. Secondary outcome measures included, as a measure of safety, perioperative events such as paresthesias. Postoperative complications were also noted. Fourteen patients (7 female) were included in the study. All patients had undergone a T12-L2 osteoplastic laminoplasty and bilateral L1-S1 VDR. Nine patients had quadriplegic mixed hypertonia, 4 had quadriplegic spasticity, and 1 had generalized secondary dystonia. Following VDR, there was a significant decrease in both lower-extremity modified Ashworth Scale (mAS) scores (mean difference [MD] -2.77 ± 1.0, p < 0.001) and upper-extremity mAS scores (MD -0.71 ± 0.76, p = 0.02), with an average follow-up of 3 months. In the patient with generalized dystonia, the lower-extremity Barry-Albright Dystonia Scale score decreased from 8 to 0, and the overall score decreased from 32 to 13. All parents noted increased ease in caregiving, particularly in terms of positioning, transfers, and changing. The mean daily enteral baclofen dose decreased from 47 mg preoperatively to 24.5 mg postoperatively (p < 0.001). Three patients developed wound dehiscence, 2 of whom had concurrent infections. Lumbosacral VDR is safe, is effective for tone control, and can provide quality of life improvements in patients with medically refractory lower-limb mixed hypertonia. Lumbosacral VDR can be considered for palliative tone control in nonambulatory patients with more severe CP. Larger studies with longer follow-ups are necessary to further determine safety and long-term benefits in these patients.

Long-term use of intrathecal baclofen reduces neuropathic pain and its interference with general activity in spinal cord injury individuals.

Long-term analgesic effect of intrathecal baclofen was reported in individuals with spinal cord injury. We conducted a prospective study to evaluate the effect of intrathecal baclofen on subtypes of neuropathic pain and its interference with general activity. Nine spinal cord injury individuals who presented with severe spasticity and moderate to severe neuropathic pain received intrathecal baclofen via an implanted pump. We applied the ASIA Impairment Scale to assess spinal cord injury severity. Neuropathic pain was evaluated by numerical rating scale, Neuropathic Pain Symptom Inventory, and Brief Pain Inventory. Evaluations were performed at baseline and after at least 6months of continuous intrathecal baclofen treatment. Intrathecal baclofen led to significant pain reduction as measured by numerical rating scale, Neuropathic Pain Symptom Inventory, and Brief Pain Inventory (p < 0.05). Improvements were significant for paroxysmal pain and dysesthesia and for pain interference with general activity, as assessed by the Brief Pain Inventory (p < 0.05). There was a significant relationship between the time since spinal cord injury and changes in paroxysmal pain as well as in the total Neuropathic Pain Symptom Inventory score (p < 0.05). The baclofen dose correlated also to the percentage changes in neuropathic pain improvement and sleep (p < 0.003). The present results provide evidence that intrathecal baclofen effectively reduces neuropathic pain, particularly paroxysmal pain and dysesthesia, and improves pain interference and overall well-being in individuals with spinal cord injury. Clinicians should be aware of this less well-known beneficial effect of intrathecal baclofen and should consider such a treatment option for better control of neuropathic pain in individuals with spinal cord injury.

Intrathecal baclofen efficacy for managing motor function and spasticity severity in patients with cerebral palsy: a systematic review and meta-analysis

BackgroundSpasticity can significantly affect a patient’s quality of life, caregiver satisfaction, and the financial burden on the healthcare system. Baclofen is one of only a few options for treating spasticity. The purpose of this study is to investigate the impact of intrathecal baclofen (ITB) therapy on severe40.23 spasticity and motor function in patients with cerebral palsy.MethodsWe conducted a systematic review in PubMed, Scopus, Ovid, and the Cochrane Library in accordance with the PRISMA guidelines. We included studies based on eligibility criteria that included desired participants (cerebral palsy patients with spasticity), interventions (intrathecal baclofen), and outcomes (the Ashworth scales and the Gross Motor Function Measure [GMFM]). The within-group Cohen’s d standardized mean differences (SMD) were analyzed using the random effect model.ResultsWe screened 768 papers and included 19 in the severity of spasticity section and 6 in the motor function section. The pre-intervention average spasticity score (SD) was 3.2 (0.78), and the post-intervention average score (SD) was 1.9 (0.72), showing a 40.25% reduction. The SMD for spasticity reduction was − 1.7000 (95% CI [-2.1546; -1.2454], p-value < 0.0001), involving 343 patients with a weighted average age of 15.78 years and a weighted average baclofen dose of 289 µg/day. The SMD for the MAS and Ashworth Scale subgroups were − 1.7845 (95% CI [-2.8704; -0.6986]) and − 1.4837 (95% CI [-1.8585; -1.1088]), respectively. We found no relationship between the participants’ mean age, baclofen dose, measurement time, and the results. The pre-intervention average GMFM (SD) was 40.03 (26.01), and the post-intervention average score (SD) was 43.88 (26.18), showing a 9.62% increase. The SMD for motor function using GMFM was 0.1503 (95% CI [0.0784; 0.2223], p-value = 0.0030), involving 117 patients with a weighted average age of 13.63 and a weighted average baclofen dose of 203 µg/day. In 501 ITB implantations, 203 medical complications were reported, including six new-onset seizures (2.96% of medical complications), seven increased seizure frequency (3.45%), 33 infections (16.26%), eight meningitis (3.94%), and 16 cerebrospinal fluid leaks (7.88%). Delivery system complications, including 75 catheter and pump complications, were also reported.ConclusionDespite the risk of complications, ITB has a significant impact on the reduction of spasticity. A small but statistically significant improvement in motor function was also noted in a group of patients.

Characteristics of Changes in Intrathecal Baclofen Dosage over Time due to Causative Disease.

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.

Long-term results on the suppression of secondary brain injury by early administered low-dose baclofen in a traumatic brain injury mouse model

Secondary injury from traumatic brain injury (TBI) perpetuates cerebral damages through varied ways. Attenuating neuroinflammation, which is a key feature of TBI, is important for long-term prognosis of its patients. Baclofen, a muscle relaxant, has shown promise in reducing excessive inflammation in other neurologic disorders. However, its effectiveness in TBI remains ambiguous. Thus, our study aimed to investigate whether early administration of baclofen could elicit potential therapeutic effects by diminishing exaggerated neuroinflammation in TBI mice. In this study, 80 C57BL/6 mice were used, of which 69 mice received controlled cortical impact. The mice were divided into six groups (11–16 mice each). Baclofen, administered at dose of 0.05, 0.2 and 1 mg/kg, was injected intraperitoneally a day after TBI for 3 consecutive weeks. 3 weeks after completing the treatments, the mice were assessed histologically. The results showed that mice treated with baclofen exhibited a significantly lower volume of lesion tissue than TBI mice with normal saline. Baclofen also reduced activated glial cells with neurotoxic immune molecules and inhibited apoptotic cells. Significant recovery was observed and sustained for 6 weeks at the 0.2 mg/kg dose in the modified neurological severity score. Furthermore, memory impairment was recovered with low-doses of baclofen in the Y-maze. Our findings demonstrate that early administration of low dose baclofen can regulate neuroinflammation, prevent cell death, and improve TBI motor and cognitive abnormalities.

Complications of Intrathecal Baclofen Pump Therapy: An Institutional Experience from Saudi Arabia.

The intrathecal baclofen pump (ITB) is one of the advanced treatment options in the management of spasticity. This retrospective cohort study was conducted to identify the complications of ITB treatment at a tertiary care rehabilitation facility. Various demographic and technical factors were analyzed, which are less often reported in the literature. All patients with ITB who had their refill at the ITB clinic between November 2019 and March 2020 were included. Of 48 patients, 17 patients had 18 (37.5%) ITB-related complications. Catheter-related complications were most common, whereas loss of efficacy (16.7%) and baclofen withdrawal (14.5%) were the most common outcomes of complications. Only catheter occlusion had a significant relationship with the pattern of spastic quadriparesis (p = 0.001). Gender, rehabilitation diagnosis, patients' residence, and facility of ITB placement did not have significant association. Similarly, age, distance from hospital, disease onset, ITB therapy duration, and baclofen dose were not statistically significant in relation to ITB-related complications.

The patients with intrathecal baclofen pump in the age of COVID-19: a single center study

Purpose Intrathecal baclofen pump treatment is employed in the treatment of various diseases. Despite the benefits of intrathecal baclofen pump, patients may occasionally encounter severe complications. These complications may necessitate urgent assessment or intervention for patients with intrathecal baclofen pumps. This study aimed to evaluate the intrathecal baclofen pump-related problems, the utilization of health services, physical-psychosocial status, and the quality of life of patients with intrathecal baclofen pumps during the coronavirus disease 2019 pandemic. Materials and methods We conducted a cross-sectional, phone-based survey study between 1 June 2021 and 15 July 2021 with a sample of 23 patients with intrathecal baclofen pumps. The patients’ quality of life before the implantation of the pump, after one year of implantation, and during the pandemic was evaluated with the 3-level version of EQ-5D. Results Catheter migration developed in one of the patients, after which the pump was changed. While the dose of baclofen was altered in eight (38.1%) patients during the pandemic period, the filling period was modified in three (14.3%) patients. While 61.9% of the patients reported that their general health, mobility, spasticity and joint mobility were worse than before the pandemic, 90.5% of the patients stated that their communication and mood were worse than before the pandemic. The 3-level version of EQ-5D and EQ-Visual Analogue Scale scores of the patients were significantly decreased during pandemic (p < .05). Conclusions Due to the complications of the intrathecal baclofen pump, its management should continue uninterruptedly during the pandemic period.

Overtime Histological Changes in the Lungs after Intoxication with Baclofen Alone or in Combination with Ethanol (Experimental Study)

The aim of the study was to evaluate the overtime histological changes in the lungs after intoxication with baclofen alone or in combination with ethanol.Materials and methods. The experiment was carried out on 35 male Wistar rats weighing 290-350 g and aged 20 weeks. The animals were split into 7 equal groups (n=5); test drugs were administered via nasogastric tube: rats from Groups 1, 3 and 5 were treated with baclofen at 85 mg/kg; rats from Groups 2, 4 and 6 received similar dose of baclofen and 40% alcohol by volume at a dose of 7 ml/kg; control group rats were not administered with any drugs. Animals of all groups were removed from the experiment by cervical dislocation under anesthesia (chlorolase) after 3 hours (Groups 1, 2), 4.5 hours (Groups 3, 4) and after 24 hours (Groups 5, 6, and the controls). Lung tissue samples were examined by light microscopy. The nonparametric Kraskel-Wallis test was used for multiple comparisons between the groups, and nonparametric Mann–Whitney test with Bonferroni correction was used for pairwise comparison.Results. Light microscopy showed no pathological changes in the lungs of the Control group animals. Baclofen alone, or in combination with ethanol caused significant circulatory disorders (venular and capillary fullness, hemorrhages in the interalveolar septa (IAS) and alveoli, sludge phenomenon), emphysema, atelectasis and distelectasis, and pulmonary edema. IAS thickness in rats from all experimental groups was different from that in animals from the Control group, all differences confirmed by the Kruskel-Wallis test: H=748, p=0.00001.In Group 1 animals IAS was 44.2% thinner (p=0.00052) vs the control Group, while in all remaining experimental groups it was, on the contrary, thicker: in Group 2 – 57.6% increase in thickness (p=0.000038), in Group 3 – 99 % (p=0.00001), in Group 4 – 2.2-fold increase (p= 0.00001), in Group 5 – 2.1-fold (p= 0.00001), in Group 6 – 2.5-fold increase (p= 0.00001). Most significant increase in IAS thickness (6-fold, p=0.00001) occurred within the period from 3 to 4.5 hours after administration of baclofen, while within the period from 4.5 to 24 hours no statistically significant increase occurred (p=0.99). Co-administration of baclofen and ethanol caused 2.8-fold (p=0.00001) increase in IAS thickness after 3 hours as compared to the effects of baclofen only. IAS thickness at 4.5 hours after baclofen and ethanol co-administration increased by additional 41.8% as compared to thickness at 3 hours (p=0.00001). IAS became 11.8% thicker at 24 hours vs 4.5 hours (p=0.87). At 24 hours IAS was 21.7% (p= 0.0011) thicker after baclofen and ethanol co-administration vs baclofen alone. The alveoli size increased by 69.4% (p=0.00001) in Group 1 animals vs the Control group, by 14.3% (p=0.43) - in Group 2, by 55% (p=0.00004) - in Group 3, by 26.3% (p=0.002) - in Group 4, by 45% (p=0.0003) - in Group 5 (baclofen, 24 h), by 43.3% (p=0.0004) – in Group 6 (baclofen and ethanol, 24 h). Co-administration of baclofen and ethanol initially caused a slight increase in alveoli size, bur 3 hours later there was a visible shrinkage in the diameter of alveoli by 32.5% (p= 0.003) vs baclofen mono, 4.5 hours later – by 18.5% (p= 0.062), and 24 hours later – by 1.2% (p= 0.99), that is, the differences were leveled.Conclusion. The combined effects of baclofen and ethanol induce more severe alterations in pulmonary tissue compared to baclofen alone. The pathological changes in the lungs reached their maximum by 24 hours, which confirmed by morphometric assessment. Morphological changes in pulmonary tissue alongside with established chemical properties of the two agents can be used to diagnose cases of intoxication either with baclofen alone or in combination with ethanol.

The Effect of the Toxic Dose of Baclofen on Selected Parameters of the Cardiovascular and Respiratory Systems.

The effect of the toxic dose of the muscle relaxant baclofen on the parameters of the cardiovascular and respiratory systems was studied in adult male Wistar rats (n=20). Systolic and diastolic BP, HR, and respiratory rate were measured; histological changes in the lungs 3, 4.5, and 24 h after drug administration. Baclofen was administered orally in a sublethal toxic dose of 85 mg/kg under anesthesia. Cardiac activity was analyzed using RSM physiological indicators monitoring system with MouseMonitor S (Indus Instruments) software. Histological examination was performed by light microscopy. Baclofen significantly decreased the respiratory rate and increased HR and BP. Histological examination of the lungs revealed a complex of general pathological processes, such as local circulatory disorders (venular and capillary fullness, sludge), leukocyte infiltration of the interalveolar septa and their thickening due to edema. These findings can be used to estimate the time elapsed after baclofen treatment.

Does the Intrathecal Baclofen Dose Need to Be Changed after Spinal Fusion Surgery for Neuromuscular Scoliosis?

Patients with cerebral palsy (CP) may receive intrathecal baclofen (ITB) to reduce muscle spasticity and dystonia. It can be challenging to identify the proper dose of ITB, and anecdotally these dosing needs may change after spinal fusion surgery. This study aimed to evaluate the need for changes in ITB dosing following a spinal fusion in pediatric neuromuscular scoliosis (NMS) patients and identify predisposing factors for those changes. This was a retrospective case-control study of NMS patients with an ITB pump who later received a spinal fusion surgery. Dosing changes and the indications for the changes were postoperatively noted. Demographics, preoperative factors, and surgical factors were evaluated for correlation with dosing changes. A total of 49 patients were included in this study. Most had no change in ITB dose (71.4%), and others required a change that averaged about 10%. Male patients, those with larger pumps, and those that had a longer hospital stay were more likely to require a decrease in dose. Complications were similar between groups. Three catheters were revised during surgery: two continued on the same dose and one required an increase in dose after surgery. Spinal fusion after ITB pump placement is feasible and safe. Most patients did not require dosing changes after spine fusion; however, careful evaluation postoperatively remains prudent.

Twenty years of intrathecal baclofen therapy in Slovenia: a retrospective single-center analysis of complications.

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.

Assessment of Health Care Costs and Total Baclofen Use Associated With Targeted Drug Delivery for Spasticity

BackgroundChronic spasticity causes significant impairment and financial burden. Oral baclofen, the first-line therapy, can have intolerable, dose-dependent side effects. Targeted drug delivery (TDD) through intrathecal baclofen delivers smaller amounts of baclofen into the thecal sac via an implanted infusion system. However, the health care resource utilization of patients with spasticity receiving TDD has not been studied extensively. Materials and MethodsAdult patients who received TDD for spasticity between 2009 and 2017 were identified using the IBM MarketScan® data bases. Patients’ use of oral baclofen and health care costs were examined at baseline (one year before implantation) and three years after implantation. A multivariable regression model using the generalized estimating equations method and a log link function was used to compare postimplantation costs with those at baseline. ResultsThe study identified 771 patients with TDD for medication analysis and 576 for cost analysis. At baseline, the median costs were $39,326 (interquartile range [IQR]: $19,526–$80,679), which increased to $75,728 (IQR: $44,199–$122,676) in year 1, decreased to $27,160 (IQR: $11,896–$62,427) in year 2, and increased slightly to $28,008 (IQR: $11,771–$61,885) in year 3. In multivariable analysis, the cost was 47% higher than at baseline (cost ratio [CR] 1.47, 95% CI: 1.32–1.63) in year 1 but was 25% lower (CR 0.75, 95% CI: 0.66–0.86) in year 2 and 32% lower (CR 0.68, 95% CI: 0.59–0.79) in year 3. Before implant, 58% of patients took oral baclofen, which decreased to 24% by year 3. The median daily baclofen dose decreased from 61.8 mg (IQR: 40–86.4) before TDD to 32.8 mg (IQR: 30–65.7) three years later. ConclusionsOur findings indicate that patients who undergo TDD use less oral baclofen, potentially reducing the risk of side effects. Although total health care costs increased immediately after TDD, most likely owing to device and implantation costs, they decreased below baseline after one year. The costs of TDD reach cost neutrality approximately three years after implant, indicating its potential for long-term cost savings.

Activation of GABAB receptors in central amygdala attenuates activity of PKCδ + neurons and suppresses punishment-resistant alcohol self-administration in rats

Alcohol use despite negative consequences is a core phenomenon of alcohol addiction. We recently used alcohol self-administration that is resistant to footshock punishment as a model of this behavior, and found that activity of PKCδ + GABAergic neurons in the central amygdala (CeA) is a determinant of individual susceptibility for punishment resistance. In the present study, we examined whether activation of GABAB receptors in CeA can attenuate the activity of PKCδ + neurons in this region, and whether this will result in suppression of punishment- resistant alcohol self-administration in the minority of rats that show this behavior. Systemic administration of the clinically approved GABAB agonist baclofen (1 and 3 mg/kg) dose- dependently reduced punishment-resistant alcohol self-administration. Bilateral microinjections of baclofen into CeA (64 ng in 0.3 µl/side) reduced the activity of PKCδ + neurons, as measured by Fos expression. This manipulation also selectively suppressed punished alcohol self-administration in punishment-resistant rats. Expression analysis indicated that virtually all CeA PKCδ + neurons express the GABAB receptor. Using in vitro electrophysiology, we found that baclofen induced hyperpolarization of CeA neurons, reducing their firing rate in response to depolarizing current injections. Together, our findings provide a potential mechanism that contributes to the clinical efficacy of baclofen in alcohol addiction. Therapeutic use of baclofen itself is limited by problems of tolerance and need for dose escalation. Our findings support a mechanistic rationale for developing novel, improved alcohol addiction medications that target GABAB receptors, and that lack these limitations, such as e.g., GABAB positive allosteric modulators (PAM:s).

Seizure Occurring During Baclofen Monotherapy for Phenibut Withdrawal.

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. 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. 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. 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.

Baclofen for alcohol use disorder.

Baclofen for alcohol use disorder.

Inpatient GHB withdrawal management in an inner-city hospital in Sydney, Australia: a retrospective medical record review

RationaleRegular consumption of gamma-hydroxybutyrate (GHB) may result in a dependence syndrome that can lead to withdrawal symptoms. There are limited data on medications to manage GHB withdrawal.ObjectivesTo examine characteristics associated with delirium and discharge against medical advice (DAMA), in the context of implementing a GHB withdrawal management protocol at an inner-city hospital in 2020.MethodsWe retrospectively reviewed records (01 January 2017–31 March 2021), and included admissions that were ≥ 18 years of age, admitted for GHB withdrawal, and with documented recent GHB use. Admissions were assessed for demographics, medications administered, features of delirium, ICU admission, and DAMA. Exploratory analyses were conducted to examine factors associated (p < 0.2) with features of delirium and DAMA.ResultsWe identified 135 admissions amongst 91 patients. Medications administered included diazepam (133 admissions, 98.5%), antipsychotics (olanzapine [70 admissions, 51.9%]), baclofen (114 admissions, 84%), and phenobarbital (8 admissions, 5.9%). Features of delirium were diagnosed in 21 (16%) admissions. Delirium was associated with higher daily GHB consumption prior to admission, while duration of GHB use, time from presentation to first dose of diazepam, and concomitant methamphetamine use were inversely associated with delirium. DAMA occurred amongst 41 (30%) admissions, and was associated with a longer time from presentation to first dose of baclofen, while being female and receiving a loading dose of diazepam were inversely associated.ConclusionsThis study adds to the literature in support of the safety and feasibility of diazepam and baclofen for the management of GHB withdrawal. Prospective, randomised trials are required.