Abstract
TO THE EDITOR: Akathisia is one of the most common acute movement disorders, characterized by both subjective (feeling of inner restlessness and the urge to move) and objective (restless movements, usually shuffling of feet while sitting and pacing or rocking while standing) components. 1 It is commonly seen as an adverse effect of various medications including neuroleptic agents, serotonin reuptake inhibitors, calcium channel blockers, and antiemetics. 2,3 Although the mechanism of drug-induced akathisia is unknown, it may be attributed to the low activity of dopaminergic projections from the midbrain to the ventral striatum. 4
We report the case of a man who developed akathisia after taking a single dose of pregabalin. To our knowledge, there is no previous report of pregabalin-induced akathisia.
Case Report
A 58-year-old man was admitted to our department with dysesthetic symptoms in both feet and progressively worsening pain. His medications included clopidogrel 75 mg/day, metformin 1000 mg/day, and metoprolol succinate 50 mg/day for the past 10 years for coronary artery disease, diabetes, and hypertension. Initial examination revealed diminished sensitivity to pinprick tests in the fingertips and over both feet and legs up to the knee. Test results of vibratory sensitivity, muscle strength and tone, cranial nerves, mental status, and ankle jerk reflexes were normal. Results of routine laboratory investigations and electrodiagnostic testing were within normal limits.
His diagnosis was small fiber neuropathy, and pregabalin was started at 75 mg twice daily for pain control. The following day, he was admitted to our department with feelings of restlessness immediately after taking a single dose of pregabalin 75 mg. He reported anxiety with a need to continue moving to relieve the tension in his legs and an unbearable state of never being able to sit still. On the Barnes Akathisia Rating Scale (BARS), 5 he scored 2 both in the objective category (restless movement present for at least half of the observation period) and subjective category (awareness of restlessness and distress related to restlessness). The global score was 4, which indicated marked akathisia. Results of brain magnetic resonance imaging and an electroencephalogram were normal. Pregabalin was stopped and the symptoms resolved within 24 hours. His score on the BARS decreased to zero. He did not report symptoms of akathisia during the following 6 weeks. When pregabalin 75 mg twice daily was restarted, the patient returned with the symptoms of akathisia. The Naranjo probability scale indicated a probable relationship between akathisia and pregabalin therapy. 6 The patient was started on gabapentin 300 mg/day, with the dose titrated to 900 mg/day; akathisia did not return.
Discussion
Pregabalin is widely used in the management of diabetic peripheral neuropathy, postherpetic neuralgia, anxiety disorder, and partial epilepsy. 7 The main mode of action is selective inhibitory effect on voltage-gated calcium channels containing the α(2)δ-1 subunit and reduction of the synaptic release of several neurotransmitters. 8
As known, pregabalin is more potent than gabapentin. Both have been shown to increase the rate of functional γ-aminobutyric acid (GABA) transport. Therefore, the potentiation of GABAergic effects and/or inhibition of the excitatory neurotransmission might indirectly cause akathisia. Some subtle mechanisms not clearly understood may also have a role in this adverse effect. 9 β-Blockers have been studied for treatment of akathisia, and metoprolol has been used for this purpose. 10 Our patient developed akathisia even though he had been receiving metoprolol for 10 years.
Because pregabalin is widely used in clinical practice, clinicians need to consider the possibility of development of akathisia during the treatment.
Footnotes