Can selective serotonin reuptake inhibitors cause restless legs syndrome?/nThis is a general questi

Fråga: Can selective serotonin reuptake inhibitors cause restless legs syndrome?

This is a general question.

Sammanfattning: Selective serotonin reuptake inhibitors have been reported to cause, albeit rarely, or worsen restless legs syndrome. This side effect seems to be reversible after discontinuing the offending drug.

Svar: Restless legs syndrome is believed to be caused by a dysfunction in the brain dopaminergic system. It has been observed that dopamine antagonists that can penetrate the blood-brain barrier, such as metoclopramide, worsen the symptoms of restless legs syndrome. Dopamine agonists are, on the other hand, the main current treatment for restless legs syndrome (1). Selective serotonin reuptake inhibitors have some antidopaminergic characteristics and can cause extrapyramidal symptoms, such as akathisia. Clinically, akathisia can be difficult to differentiate from restless legs syndrome, which also has been named as a rare but eventual side effect of selective serotonin reuptake inhibitors (2,3,4).

There are 3 published case reports of selective serotonin reuptake inhibitors-related restless legs syndrome (fluoxetine (5), paroxetine (6) and sertraline (3)). All of those cases occurred in patients with a previous history of restless legs syndrome, raising the suspicion that, more than causing restless legs syndrome, selective serotonin reuptake inhibitors can unmask pre-existent or predisposition for restless legs syndrome. In the Swedish adverse drug reaction register there are three reported cases of restless legs syndrome in relation to selective serotonin reuptake inhibitors use, two with citalopram and one with fluoxetine (7). After the withdrawal of the offending drugs, a partial or complete remission has been observed in all cases.

The effect of selective serotonin reuptake inhibitors on patients with ongoing restless legs syndrome has also been investigated. In a questionnaire sent to 113 patients, 66 returned it, and of those, 58% reported an improvement in symptoms, 12% the abolishment of the symptoms, 30% reported no change and 12% reported worsening of the symptoms (8). Garcia-Borreguero D, Odin P, Schwarz C. Restless legs syndrome: an overview of the current understanding and management. Acta Neurol Scand. 2004 May;109(5):303-17. Schillevoort I, van Puijenbroek EP, de Boer A, Roos RA, Jansen PA, Leufkens HG. Extrapyramidal syndromes associated with selective serotonin reuptake inhibitors: a case-control study using spontaneous reports. Int Clin Psychopharmacol. 2002;17(2):75-9.

Hargrave R, Beckley DJ. Restless leg syndrome exacerbated by sertraline. Psychosomatics. 1998;39(2):177-8.
www.internetmedicin.se Restless legs syndrome (cited 2005-05-24)
Bakshi R. Fluoxetine and restless legs syndrome. J Neurol Sci. 1996;142(1-2):151-2.

Sanz-Fuentenebro FJ, Huidobro A, Tejadas-Rivas A. Restless legs syndrome and paroxetine. Acta Psychiatr Scand 1996;94(6):482-4. (abstract) Swedis (The Swedish Drug Information System) (cited 2005-05-13) Dimmitt SB, Riley GJ. Selective serotonin receptor uptake inhibitors can reduce restless legs symptoms. Arch Intern Med. 2000 Mar 13;160(5):712.