Abrupt discontinuation of intrathecal baclofen, regardless of the cause, has resulted in sequelae that include high fever, altered mental status, exaggerated rebound spasticity, and muscle rigidity, that in rare cases has advanced to rhabdomyolysis, multiple organ-system failure and death.
Prevention of abrupt discontinuation of intrathecal baclofen requires careful attention to programming and monitoring of the infusion system, refill scheduling and procedures, and pump alarms. Patients and caregivers should be advised of the importance of keeping scheduled refill visits and should be educated on the early symptoms of baclofen withdrawal. Special attention should be given to patients at apparent risk (e.g. spinal cord injuries at T-6 or above, communication difficulties, history of withdrawal symptoms from oral or intrathecal baclofen). Consult the technical manual of the implantable infusion system for additional postimplant clinician and patient information (see WARNINGS).
LIORESAL INTRATHECAL (baclofen injection) is a muscle relaxant and antispastic.
LIORESAL INTRATHECAL is indicated for use in the management of severe spasticity. Patients should first respond to a screening dose of intrathecal baclofen prior to consideration for long term infusion via an implantable pump. For spasticity of spinal cord origin, chronic infusion of LIORESAL INTRATHECAL via an implantable pump should be reserved for patients unresponsive to oral baclofen therapy, or those who experience intolerable CNS side effects at effective doses. Patients with spasticity due to traumatic brain injury should wait at least one year after the injury before consideration of long term intrathecal baclofen therapy. LIORESAL INTRATHECAL (baclofen injection) is intended for use by the intrathecal route in single bolus test doses (via spinal catheter or lumbar puncture) and, for chronic use, only in implantable pumps approved by the FDA specifically for the administration of LIORESAL INTRATHECAL into the intrathecal space.
Spasticity of Spinal Cord Origin: Evidence supporting the efficacy of LIORESAL INTRATHECAL was obtained in randomized, controlled investigations that compared the effects of either a single intrathecal dose or a three day intrathecal infusion of LIORESAL INTRATHECAL to placebo in patients with severe spasticity and spasms due to either spinal cord trauma or multiple sclerosis. LIORESAL INTRATHECAL was superior to placebo on both principal outcome measures employed: change from baseline in the Ashworth rating of spasticity and the frequency of spasms.
Spasticity of Cerebral Origin: The efficacy of LIORESAL INTRATHECAL was investigated in three controlled clinical trials; two enrolled patients with cerebral palsy and one enrolled patients with spasticity due to previous brain injury. The first study, a randomized controlled cross- over trial of 51 patients with cerebral palsy, provided strong, statistically significant results; LIORESAL INTRATHECAL was superior to placebo in reducing spasticity as measured by the Ashworth Scale. A second cross- over study was conducted in 11 patients with spasticity arising from brain injury. Despite the small sample size, the study yielded a nearly significant test statistic (p= 0.066) and provided directionally favorable results. The last study, however, did not provide data that could be reliably analyzed.
LIORESAL INTRATHECAL therapy may be considered an alternative to destructive neurosurgical procedures. Prior to implantation of a device for chronic intrathecal infusion of LIORESAL INTRATHECAL, patients must show a response to LIORESAL INTRATHECAL in a screening trial (see Dosage and Administration).
Published Studies Related to Lioresal (Baclofen Intrathecal)
Baclofen for the Treatment of Alcohol Dependence and Possible Role of Comorbid
baclofen in the treatment of alcohol dependence... CONCLUSIONS: In spite of the small sample for a 3-arm clinical trial, this study
Randomised clinical trial: arbaclofen placarbil in gastro-oesophageal reflux
disease--insights into study design for transient lower sphincter relaxation
characteristics of patients who were responders... CONCLUSIONS: Arbaclofen placarbil was not superior to placebo in the primary
Baclofen reduces binge eating in a double-blind, placebo-controlled, crossover
Baclofen has shown promise in treating substance use disorders and also reduced
binge frequency in an open-label trial...
Defining the Role of Baclofen for the Treatment of Alcohol Dependence: A Systematic Review of the Evidence. [2011.12.06]
The pharmacological properties of baclofen, a GABA(B) receptor agonist, have led to investigation of its use for the off-label treatment of alcohol dependence. Literature examining the role of baclofen in alcohol dependence suggests that it may be a useful medication in the treatment armamentarium with an additional benefit of promoting abstinence and reducing alcohol-associated cravings and anxiety...
treating alcohol withdrawal with oral baclofen: a randomized, double-blind, placebo-controlled trial. [2011.10]
BACKGROUND: Abrupt cessation of alcohol intake causes habituated drinkers to experience symptoms of alcohol withdrawal syndrome (AWS). OBJECTIVE: To determine the effect of the gamma-aminobutyric acid (GABA)-B agonist baclofen on the course of acute symptomatic AWS... CONCLUSIONS: We found that the use of baclofen was associated with a significant reduction in the use of high doses of benzodiazepine (lorazepam) in the management of symptomatic AWS. The use of low-dose baclofen in the management of AWS deserves further study, as reduced dependence on high-dose benzodiazepines in AWS management could improve patient safety. Copyright (c) 2011 Society of Hospital Medicine.
Clinical Trials Related to Lioresal (Baclofen Intrathecal)
Baclofen for Smoking Cessation in a Non-Psychiatric Population [Recruiting]
The primary hypothesis for this study is that, in nicotine-dependent tobacco smokers,
baclofen will be superior to placebo for smoking abstinence measures.
The secondary hypothesis is that subjects assigned to the baclofen groups will exhibit
higher rates of medication compliance (i. e. take the medication as directed for the trial
period) than those in the placebo group.
The tertiary hypothesis is that baclofen will lead to significant reductions in tobacco
withdrawal and craving ratings as compared to placebo.
Oral Baclofen Pharmacokinetics and Pharmacodynamics in Children With Spasticity [Recruiting]
Oral baclofen is used commonly to treat spasticity in children with cerebral palsy.
Although for adults there is dosing,safety and efficacy information in the package insert,
this is not the case for children. The purpose of this study is to determine how fast the
drug is cleared from the body, the correct dose, and long-term safety and efficacy for
children with spasticity.
Safety Study of 3 mg/mL Baclofen Injection (Intrathecal) Using A Programmable Pump [Not yet recruiting]
Oral and IV Baclofen in Adult Volunteers [Not yet recruiting]
The primary objective of this study is to characterize baclofen pharmacokinetics following
oral and intravenous administration in patients who are on chronic oral baclofen therapy.
The secondary objective is to determine the safety profile of an IV baclofen formulation.
This study is a randomized crossover study with two treatment arms. All subjects will
receive a dose of oral baclofen and a dose of IV baclofen on separate study days. Whether
the oral or intravenous form is given on the first study day will be randomized in a 1: 1
The pharmacokinetic and tolerability information gained from this study will support the
development of further studies to assess the use of IV baclofen to prevent or treat baclofen
Transcranial Magnetic Stimulation (TMS) Measures of Plasticity and Excitatory/Inhibitory Ratio as Biomarkers: R-baclofen Effects in Normal Volunteers [Recruiting]
Our overall objective is to apply Transcranial Magnetic Stimulation (TMS) to develop
measures of human synaptic plasticity and of brain excitatory: inhibitory ratio (E: I ratio),
which we propose as novel biomarkers and outcome measures that will expedite clinical trials
of treatments for Autism Spectrum Disorder (ASD). One potential therapeutic agent,
R-baclofen will be investigated under this protocol.
TMS is a safe, inexpensive and noninvasive means to focally stimulate the human brain.
Presently, TMS is in extensive use as a means to measure regional brain excitability, which
is dependent on local synaptic strength. TMS can be used to temporarily alter synaptic
strength as well as to acutely measure levels of cortical excitability and short and long
interval inhibition. Since altered synaptic plasticity and an imbalanced
inhibitory: excitatory ratio are cited as fundamental abnormalities in ASD, we hypothesize
that both severity of ASD-related learning deficits and their improvement after therapy will
correlate with TMS measures of synaptic plasticity and E: I ratio. We propose to embed TMS
measures of synaptic plasticity and E: I ratio in a 'Proof of Principal' trial of R-baclofen
and to examine:
Aim 1: Whether R-baclofen (a potential therapeutic agent for ASD) predictably alters TMS
measures of synaptic plasticity and E: I ratio as a function of plasma concentration in adult
volunteers. We will test the following hypotheses:
1. R-baclofen produces a significant change in TMS measures of LTD and E: I ratio; and
2. R-baclofen plasma levels and TMS measures of LTD and E: I ratio show a predictable
Exploratory Aim 1: Whether the presence of genetic polymorphisms of the BDNF and GABA-B
receptor genes has a moderating effect on TMS measures and on R-baclofen effects. We will
test the following hypotheses:
1. Presence of the BDNF val66met allele will be associated with decreased long-term
depression (LTD) of cortical excitability
2. Polymorphisms of GABA-B receptor genes will be associated with altered magnitude of
response to R-baclofen as measured by TMS
Reports of Suspected Lioresal (Baclofen Intrathecal) Side Effects
Muscle Spasticity (125),
Drug Withdrawal Syndrome (82),
Condition Aggravated (71),
Implant Site Infection (61),
Implant Site Effusion (55),
Muscle Spasms (52),
Medical Device Complication (47),
Device Dislocation (44),
Overdose (44), more >>