Baclofen therapeutics, toxicity, and withdrawal: A narrative review

Abstract

Baclofen is an effective therapeutic for the treatment of spasticity related to multiple sclerosis, spinal cord injuries, and other spinal cord pathologies. It has been increasingly used off-label for the management of several disorders, including musculoskeletal pain, gastroesophageal reflux disease, and alcohol use disorder. Baclofen therapy is associated with potential complications, including life-threatening toxicity and withdrawal syndrome. These disorders require prompt recognition and a high index of suspicion. While these complications can develop following administration of either oral or intrathecal baclofen, the risk is greater with the intrathecal route. The management of baclofen toxicity is largely supportive while baclofen withdrawal syndrome is most effectively treated with re-initiation or supplementation of baclofen dosing. Administration of other pharmacologic adjuncts may be required to effectively treat associated withdrawal symptoms. This narrative review provides an overview of the historical and emerging uses of baclofen, offers practical dosing recommendations for both oral and intrathecal routes of administration, and reviews the diagnosis and management of both baclofen toxicity and withdrawal.

Multiple Electroencephalogram Recordings for Monitoring the Evolution of Neurological Complications during Baclofen Withdrawal Syndrome

“…The recent expansion in the use of baclofen to treat spasticity of different causes has been associated with a significant increase in its complications, including toxicity events and withdrawal syndrome, especially regarding intrathecal baclofen administration [3]. In particular, withdrawal syndrome is observed frequently after sudden cessation of intrathecal baclofen administration mainly due to pump malfunction, migration of the intrathecal catheter, or, as in our case, removal of the pump after infection [10,11].…”

“…Baclofen, an agonist for gamma-aminobutyric acid (GABA) receptors [1], is an effective therapeutic mainly for the treatment of spasticity related to spinal cord injuries, other spinal cord diseases, and multiple sclerosis [2]. In recent years, however, as its clinical use has increased-such as for treatment of musculoskeletal pain and muscle spasm-its poten-tial side effects, including life-threatening toxicity and withdrawal syndrome, have become more frequent [3]. Baclofen toxicity and withdrawal syndrome, especially when related to intrathecal administration, can often determine severe multisystem organ failure requiring admission to the intensive care unit (ICU) to administer supportive measures to ensure vital sign stability.…”

“…Baclofen toxicity and withdrawal syndrome, especially when related to intrathecal administration, can often determine severe multisystem organ failure requiring admission to the intensive care unit (ICU) to administer supportive measures to ensure vital sign stability. Moreover, neurological signs such as seizures [4,5], encephalopathy [6], and altered mental status are common to both the syndromes [3]. However, while the electroencephalographic (EEG) patterns detected during baclofen toxicity syndrome have been reported widely in the literature [4,7,8], the EEG patterns related to the sudden cessation of baclofen administration-leading to withdrawal syndrome-and thus supporting the effective clinical diagnosis of seizures or encephalopathy have not been described.…”

In Support of Initial Parenteral Medical Management of Intrathecal Baclofen Withdrawal in Spasticity Patients

“…7,34 Thus, the clear first-line option for treatment is parenteral therapy. 35 The parenteral agent with which the most experience has been gained is diazepam.…”

Low-Dose Baclofen-Induced Encephalopathy in a Healthy Young Adult: Is Baclofen Toxicity Dose-Dependent?

“…Studies suggested that toxicity is likely dose-dependent and more common at doses greater than 200mg [4,5]. It is worth noting that severe baclofen withdrawal may occur within hours to days of sudden cessation or dose reduction and is mostly associated with altered mental status, hallucinations, worsening spasticity, and fever [6] The usual maximum daily dose of oral baclofen is 80mg [1], although some patients require up to 120mg/day [7]. Toxicity with high doses is seen in accidental or intentional overdose and patients requiring intrathecal baclofen [3].…”