Pregabalin associated asterixis.

To the Editor: We read with great interest the article of Babiy et al. on asterixis (negative myoclonus) related to gabapentin as a cause of falls. The authors present an important observation on a presumably underestimated pharmacologic side effect of gabapentin. In addition, they succeeded splendidly in giving a comprehensive overview on the topic of falls and positive and negative myocloni. From the literature, it is well known that gabapentin can cause a number of neurological side effects, such as dizziness, ataxia, and sleepiness, which are often dose-dependent and mostly transient. However, pronounced positive myocloni, movement disorders such as oculogyric crisis, dystonia, chorea (our own unpublished observations), or even asterixis, as described by the authors, often lead to discontinuation and failure of treatment. Recently, pregabalin was introduced as a new GABA-ergic drug in clinical practice with similar indications as gabapentin for the treatment of epilepsy and neuropathic pain. We recently cared for a 89-yr-old woman who developed severe asterixis after intake of 150 mg of pregabalin twice daily for the treatment of postherpetic pain. Clinically, she showed prominent negative myoclonus in all her limbs, which was slightly stronger in the upper limbs. The asterixis severely impaired her standing and walking and also led to recurrent falls, necessitating hospitalization. Other causes for asterixis such as metabolic disorders, focal brain lesions, and inflammation were excluded by laboratory tests, cerebrospinal fluid analysis, and computed tomography. The patient’s co-medication included 10 mg of ramipril, 10 mg of torasemid, and 20 mg of omeprazole, which were unchanged within the preceding months and prescribed for arterial hypertension and erosive gastritis. Discontinuation of pregabalin led to rapid improvement of the asterixis. Two days later, the patient was able to stand and walk without support and regained self-dependency in activities of daily life. Pain management was continued with opioids (tramadol) and metamizol. Considering that, pharmacologically, pregabalin acts similarly to gabapentin, comparable side effects of both drugs can be expected. Thus, pregabalin-related positive myoclonus has been observed but hitherto not asterixis (negative myoclonus). Unfortunately, in our patient, diagnosis of asterixis was based on clinical observation only. Neither electromyographic nor electroencephalographic recording could be performed in our patient because clinical symptoms resolved rapidly after discontinuation of pregabalin. However, despite the lack of an electroencephalographic recording, it is highly unlikely that the asterixis was due to an epileptic seizure because mental function was not impaired at any time. This assumption is further supported by our observation of a rapid recovery after discontinuation of pregabalin as the single therapeutic intervention. Other frequent causes of metabolic disorders provoking myocloni were excluded with high certainty. Thus, we strongly assume an association between the asterixis and the intake of pregabalin in our patient. Recently, a similar case report describes ataxia, generalized myocloni in combination with hand dystonia, and agitation during pregabalin therapy. Thus, side effects of pregabalin might cover a broader spectrum of neurological signs and symptoms than previously known. Myocloni in general have been described after the intake of gabapentin, lamotrigine, carbamazepine, oxcarbazepine, and now pregabalin. We therefore speculate that a common mechanism (e.g., electrical changes at the cerebral cell membranes with dysbalance of action potentials and transmitters) might be involved in the pathogenesis of drug-related myocloni.