Absolutely! Although we usually think of withdrawal symptoms in the setting of complete discontinuation of certain CNS depressants, even a reduced dose of baclofen^1,2 in a patient who has been on a higher dose chronically can precipitate full-blown withdrawal symptoms, such as delirium, fevers, hallucinations, hyperspasticity, autonomic instability and even respiratory failure, multiorgan failure, cardiac arrest and death.^1-5

Recall that baclofen is a GABA-B agonist and a potent inhibitor of neuronal synapses with resultant decreased excitation of muscle spindles and muscle spasticity.⁶ Similar to other benzodiazepines, baclofen is also a CNS depressant and bears many similarities with alcohol in its physiologic effects.  For example, baclofen and alcohol both produce unsteady gait, dizziness, mood alterations and impairment in attention and memory and reduce anxiety, among others.  Not surprisingly, abrupt withdrawal from baclofen may produce similar symptoms as those associated with alcohol withdrawal, such as confusion, hallucination and delirium (observed in our patient) as well as seizures.³ Withdrawal symptoms typically occur 24-48 hours after discontinuation or reduction in the dose of baclofen.^1,2

Of course, many of our hospitalized patients are already at risk of mental status changes or sedation from their underlying conditions or from medications needed to treat them.  In this setting, consideration in reducing the home dose of certain CNS depressants, such as baclofen, is understandable and reasonable. However, we should also keep in mind that even a reduction in the chronic dose of baclofen carries a risk of withdrawal!  Unfortunately, healthcare facilities often lack established management protocols for anticipated interruption of oral baclofen.⁷

In our patient, the home dose of baclofen had been reduced by one-half following his admission. Worsening delirium and new onset visual and auditory hallucinations were noted within a few days of hospitalization. Thankfully, no further bouts of confusion or hallucination was observed after resuming his home dose.

Bonus Pearl:

Did you know that baclofen is often used (off label) to treat intractable hiccups of central origin? ^8,9

Contributed by Fahad Tahir, MD, Mercy Hospital-St. Louis, St. Louis, Missouri

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References:

1. Terrence CF, Fromm GH. Complications of Baclofen Withdrawal. Arch Neurol. 1981;38(9):588–589. doi:10.1001/archneur.1981.00510090082011. https://jamanetwork.com/journals/jamaneurology/article-abstract/580084

2. O’Rourke, F., Steinberg, R., Ghosh, P., & Khan, S. (2001). Withdrawal of baclofen may cause acute confusion in elderly patients. BMJ (Clinical research ed.), 323(7317), 870.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1121408/ 

3. de Beaurepaire R. A review of the potential mechanisms of action of baclofen in alcohol use disorder. Front. Psychiatry 2018; 9:506). In fact, baclofen may be a promising treatment for alcohol use disorder. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232933/pdf/fpsyt-09-00506.pdf
   
4. Cardoso AL, Quintaneiro C, Seabra H, Teixeira C. Cardiac arrest due to baclofen withdrawal syndrome. BMJ Case Rep. 2014;2014:bcr2014204322. Published 2014 May 14.doi:10.1136/bcr-2014-204322 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025399/pdf/bcr-2014-204322.pdf

5. Green LB, Nelson VS. Death after acute withdrawal of intrathecal baclofen: case report and literature review. Arch Phys Med Rehabil. 1999 Dec;80(12):1600-4. doi: 10.1016/s0003-9993(99)90337-4. PMID: 10597813. https://www.archives-pmr.org/article/S0003-9993(99)90337-4/pdf

6. Allerton CA, Boden PR, Hill RG. Actions of the GABAB agonist, (-)-baclofen, on neurones in deep dorsal horn of the rat spinal cord in vitro. Br J Pharmacol. 1989;96(1):29-38. doi:10.1111/j.1476-5381.1989.tb11780.x https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1854300/

7. Schmitz NS, Krach LE, Coles LD, Schrogie J, Cloyd JC, Kriel RL. Characterizing Baclofen Withdrawal: A National Survey of Physician Experience. Pediatr Neurol. 2021 Sep;122:106-109. doi: 10.1016/j.pediatrneurol.2021.06.007. Epub 2021 Jul 28. PMID: 34330615. https://www.pedneur.com/article/S0887-8994(21)00129-6/fulltext

8. Zhang, C., Zhang, R., Zhang, S. et al. Baclofen for stroke patients with persistent hiccups: a randomized, double-blind, placebo-controlled trial. Trials 15, 295 (2014). https://doi.org/10.1186/1745-6215-15-295

9. Jeon YS, Kearney AM, Baker PG Management of hiccups in palliative care patients BMJ Supportive & Palliative Care 2018;8:1-6. https://spcare.bmj.com/content/8/1/1.long

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!