By Marcello Cherchi, MD PhD
For patients
Baclofen is a medication that may help with muscle spasms. It may also help some abnormal eye movements. It can cause sleepiness, weakness and other problems. It should not be taken with certain medications.
For clinicians
Overview
Baclofen is a CNS depressant that agonizes GABAB receptors. It has been FDA approved for treatment of spasticity, though has numerous off-label uses. Potential adverse effects of baclofen include hypothermia, bradycardia, hypotension, blurry vision, muscle weakness and cognitive impairment. It is preferable to avoid administering baclofen with other medications that have CNS depressant properties. In otoneurology baclofen has been tried in the management of congenital periodic alternating nystagmus, upbeat nystagmus and some forms of acquired nystagmus. Its mechanism of action is unclear; it may affect the velocity storage mechanism.
Introduction
Gamma amino butyric acid (GABA) is the most abundant inhibitory neurotransmitter in the human central nervous system. It binds to three GABA receptor subtypes (GABAA, GABAB, GABAC). Baclofen is currently the only FDA-approved agonist of GABAB receptors.
Originally designed as a derivative of GABA, baclofen was first synthesized in 1962 and intended as an anti-epileptic, though its FDA approval in 1977 was for treatment of spasticity. Its mechanism (GABAB receptor agonism) was not recognized until 1981 (Kent et al. 2020).
Baclofen has been used off-label in the management of a wide variety of disorders, including dystonias and other movement disorders, alcohol withdrawal, neuralgia and migraine.
Adverse effects
Baclofen is a CNS depressant, and as such it can induce symptoms such as hypothermia, bradycardia, hypotension, blurry vision, muscle weakness and cognitive impairment.
Contraindications
One should avoid administering baclofen with other medications that have CNS depressant properties (e.g., opiates and other analgesics, tricyclic compounds), particularly other GABA‑ergic medications (e.g., benzodiazepines, barbiturates, many sleep-promoting medications). Baclofen may also be relatively contraindicated in certain psychiatric disorders (e.g., depression, bipolar disorder, schizophrenia).
Relevance in otoneurology
Baclofen has limited application in otoneurology. It has been studied in various forms of nystagmus, including several forms of acquired nystagmus (Averbuch-Heller et al. 1997), congenital periodic alternating nystagmus (Comer et al. 2006; Isago et al. 1985; Plant 1982; Solomon et al. 2002) and upbeat nystagmus (Dieterich et al. 1991).
The mechanism by which baclofen influences these forms of nystagmus is unclear. Some literature suggests that baclofen affects the function of the velocity storage mechanism (Cohen et al. 1987).
References
Averbuch-Heller L, Tusa RJ, Fuhry L, Rottach KG, Ganser GL, Heide W, Buttner U, Leigh RJ (1997) A double-blind controlled study of gabapentin and baclofen as treatment for acquired nystagmus. Ann Neurol 41: 818-25. doi: 10.1002/ana.410410620
Cohen B, Helwig D, Raphan T (1987) Baclofen and velocity storage: a model of the effects of the drug on the vestibulo-ocular reflex in the rhesus monkey. J Physiol 393: 703-25.
Comer RM, Dawson EL, Lee JP (2006) Baclofen for patients with congenital periodic alternating nystagmus. Strabismus 14: 205-9. doi: 10.1080/09273970601026045
Dieterich M, Straube A, Brandt T, Paulus W, Buttner U (1991) The effects of baclofen and cholinergic drugs on upbeat and downbeat nystagmus. J Neurol Neurosurg Psychiatry 54: 627-32. doi: 10.1136/jnnp.54.7.627
Isago H, Tsuboya R, Kataura A (1985) A case of periodic alternating nystagmus: with a special reference to the efficacy of baclofen treatment. Auris Nasus Larynx 12: 15-21.
Kent CN, Park C, Lindsley CW (2020) Classics in Chemical Neuroscience: Baclofen. ACS Chem Neurosci 11: 1740-1755. doi: 10.1021/acschemneuro.0c00254
Plant GT (1982) Periodic alternating nystagmus in a case of hereditary ataxia and its treatment with baclofen. J Neurol Neurosurg Psychiatry 45: 1170-1. doi: 10.1136/jnnp.45.12.1170
Solomon D, Shepard N, Mishra A (2002) Congenital periodic alternating nystagmus: response to baclofen. Ann N Y Acad Sci 956: 611-5.
