Baclofen Toxicity Causing Acute, Reversible Dyskinesia

Abstract

The following unique case demonstrates an episode of acute dyskinesia secondary to oral baclofen toxicity. We discuss an 80-year-old man with a history of Stage III chronic kidney disease, coronary artery disease, diabetes and stroke who presented to the Emergency Department with new onset of behavioral changes and irregular jerking movements. The patient had been recently prescribed baclofen 10mg twice daily for a back strain he suffered; he subsequently was admitted to the hospital, and his symptoms resolved within 48 hours of admission and discontinuance of baclofen.Keywords Oral baclofen toxicity . Acute dyskinesia . Neurologic adverse effects . Reduced GFR QuestionAn 80-year-old man with a medical history of stage III chronic kidney disease, coronary artery disease, diabetes, and stroke was prescribed a new medication for a low back sprain and developed the condition shown in the following video. What is the etiology of the patient's clinical presentation? Clinical NarrativeAn 80-year-old man with history of stage III chronic kidney disease, coronary artery disease, diabetes, and stroke presented to the emergency department with new onset of behavioral changes and irregular jerking movements. He had been recently prescribed baclofen 10 mg twice daily for a back strain suffered 1 week prior and was taking it as prescribed. Other prescribed medications included aspirin 81 mg daily, vitamin D3 2000 units daily, clopidogrel bisulfate 75 mg daily, insulin aspart, 8 units with breakfast, 14 with lunch, and 12 with dinner, insulin glargine 35 units daily, lisinopril 2.5 mg daily, loratadine 10 mg daily, magnesium 84 mg daily, metoprolol 12.5 mg twice daily, pravastatin sodium 20 mg daily, prednisone 7.5 mg daily, and sitagliptin phosphate 50 mg daily.Physical examination revealed continuous, involuntary flexion, and extension movements of the upper and lower extremities, as well as repeated, involuntary turning of the head. A serum baclofen concentration measured upon presentation was 0.16 mcg/mL (0.08-0.40 mcg/mL). The patient was admitted to the hospital, and his symptoms resolved within 48 h of admission and discontinuance of baclofen. None of his routinely prescribed medications was changed or found to have known interactions with baclofen, and no other acute medical condition was revealed.This unique case demonstrates an episode of acute dyskinesia secondary to oral baclofen toxicity. Baclofen is a gamma-amino butyric acid (GABA) derivative that acts as an agonist at the GABA B receptor inducing presynaptic motor neuron inhibition and a central antispastic response [1]. While baclofen has been used primarily to limit spasticity in spinal cord disorders, it also has been studied as an inhibitor of dopamine reward pathways to treat drug abuse [2]. Baclofen is lipophilic, readily crosses the blood-brain barrier, has an elimination half-life of approximately 2 to 6 hours, and primarily is

A Case Report of Baclofen- and Clozapine-Induced Dyskinesia: A Movement Disorder

“…Some rodent models have shown that GABA receptors are expressed on both dopaminergic and GABAergic neurons [7]. Therefore, exposure to baclofen may cause activation of GABA receptors and inhibit the release of both GABAergic and dopaminergic neuron activity, modifying the release of both GABA and dopamine [7]. So hence we theorize that in our case, a combination of baclofen and clozapine resulted in enhanced, diminished dopaminergic activity.…”

“…Our patient has been taking baclofen and clozapine for his neuropathic pain and physiologic tremor, respectively, for the last 30 years. Baclofen, a muscle relaxant, acts as a GABA receptor agonist, decreasing excitatory neurotransmitter release from presynaptic terminals [7]. It is the drug of choice in treating multiple sclerosis, spinal cord injuries, and other musculoskeletal disorders [8].…”

“…The exact mechanism of baclofen and clozapine-induced dyskinesia is poorly understood. It has been hypothesized that relative dopaminergic hypofunction caused by second-generation antipsychotic clozapine may be augmented by baclofen [7]. Some rodent models have shown that GABA receptors are expressed on both dopaminergic and GABAergic neurons [7].…”

“…It has been hypothesized that relative dopaminergic hypofunction caused by second-generation antipsychotic clozapine may be augmented by baclofen [7]. Some rodent models have shown that GABA receptors are expressed on both dopaminergic and GABAergic neurons [7]. Therefore, exposure to baclofen may cause activation of GABA receptors and inhibit the release of both GABAergic and dopaminergic neuron activity, modifying the release of both GABA and dopamine [7].…”

Erratum to: Baclofen Toxicity Causing Acute, Reversible Dyskinesia

“…The video for the baclofen dyskinesia case [1] is here. We apologize the video link was not included in our December 2016 issue.…”