Fluoxetine and restless legs syndrome

Fluoxetine and restless legs syndrome

JOUHNALOFTHE NEUROLOGICAL SCIENCES Juurmd of the Neurological Sciences 142( 1996)151-152 Case report Fluoxetine and restless legs syndrome Rohit Ba...

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JOUHNALOFTHE

NEUROLOGICAL SCIENCES Juurmd of the Neurological Sciences 142( 1996)151-152

Case report

Fluoxetine and restless legs syndrome Rohit Bakshi * uni[er,ri~ &Paylm~nt Of”N~urO[vg~,

of California, Los Angeles, UCL4 School @Mcdi6ine und UCLA Medical Center, Los Angeles,CA,USA Received 22 April 1996; accepted 26 May 1996

Keywords: Fluoxetine; Restless legs syndrome; Restlessness; Ekbom’s syndrome

Fluoxetine is a selective serotonin reuptake inhibitor commonly prescribed worldwide for the treatment of depression. It has been associated with several neurological adverse reactions, including anxiety, sexual dysfunction, inappropriate secretion of antidiuretic hormone, and various extrapyramidal side effects (Coulter and Pillans, 1995; Gram, 1994). Among the myriad of complications, a relationship between fluoxetine and pre-existing restless legs syndrome (Ekbom, 1960) has not been previously described. A patient has come to my attention who developed a dose-dependent exacerbation of pre-existing, mild restless legs syndrome requiring discontinuation of fluoxetine. Case report. A 22-year-old woman presented with complaints of an episodic problem with discomfort of both legs. She reported an approximately weekly, annoying sensation of ‘restlessness’ of the legs, which would lead to an irresistible need to rub or move them. The symptoms would typically develop while seated or supine, such as while lying in bed to sleep, taking a long automobile ride, or sitting at a movie theater, nearly always in the late evening or night. Leg movements, such as flexion, stretching, bicycling motions, standing or pacing would provide relief. She denied hypomania, jitteriness, tremulousness, or generalized restlessness. The symptoms arose two weeks after she began taking fluoxetine (20 mg per day) for depression and became considerably worse after the dose was increased to 40 mg per day. She recalled as an adolescent having similar problems with restlessness of the legs which were considerably more mild, occurring no more frequently than monthly, and not prompting medical attention. For the past decade, since her late teenage years,

* Corresponding author. Present address: Department of Neurology, State University of New York at Buffalo, 3 Gates Circle, Buffalo, NY 14209, USA. Tel: + 1 (716) 887-4437; Fax: + 1 (716) 887-4440.

she had experienced these symptoms rarely, resulting in minimal, tolerable discomfort per episode. Other than taking oral contraceptives for the past six years, she denied taking any medications. There was no history of exposure to neuroleptics. She denied other medical problems or substance abuse. General physical and neurological examination were entirely unremarkable. There was no evidence for parkinsonism, neuropathy, or radiculopathy. Serum studies were unremarkable, including complete blood count, electrolytes, magnesium, blood urea nitrogen, creatinine, transaminases, vitamin B *Z,folate, iron, total iron binding capacity, ferritin, and thyroid stimulating hormone. Approximately one month later, fluoxetine was increased to 60 mg per day for the treatment of depression. She again came to my attention one week later, noting an even more severe restlessness of the legs which began occurring daily, Polysomonography was recommended, but the patient preferred a medication change. In consultation with her psychiatrist, fluoxetine was discontinued and she was kept free of medications. Six weeks later, she reported a near resolution of restlessness in the legs. During the next three years of observation, she has remained medication-free. The restlessness occurs only rarely (every few months) and the episodes are mild. She has not been re-challenged with fluoxetine or other psychotropic medications. Discussion. This patient developed the clinical features of restless legs syndrome (RLS), a neurological entity first described by Ekbom (1960). This condition developed during adolescence and then became mild during early adulthood. However, after beginning fluoxetine therapy for depression, her symptoms of RLS recurred and escalated with increasing doses. After discontinuation of fluoxetine, the symptoms improved promptly, and the patient’s RLS symptoms became infrequent. Other known precipitant of

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RLS were excluded, including iron, ferritin or folate deficiency, electrolyte disturbances, uremia, and neuropathy (Lang, 1993). It could be argued that rather than an exacerbation of RLS, my patient developed acute akathisia, a well-known adverse effect related to fluoxetine (Lipinski et al., 1989). However, her restlessness was worse while supine, isolated to the legs, and occurred nocturnally, consistent with RLS (Ekbom, 1960). Although leg restlessness may occur as part of acute akathisia, she had no additional features of akathisia, such as generalized restlessness, dysphoria, impatience, irritability, or jitteriness. Akathisia involves less conspicuous limb sensations and is present at all times of the day, and often is most prominent while the patient is standing (Lang, 1993). In addition, my patient had pre-existing, mild RLS before being exposed to fluoxetine which did not fully resolve three years after its discontinuation. Therefore, it is likely that this case represents fluoxetineinduced exacerbation of mild RLS, rather than acute akathisia. Other psychoactive medications have been associated with RLS, including cimetidine (O’Sullivan and Greenberg, 1993), anticonvulsants (Milne, 1992), and lithium (Terao et al., 1991). The mechanism of the exacerbation of RLS by fluoxetine remains speculative. Several other similar extrapyramidal side effects, such as akathisia, tremor, dyskinesias, and dystonia have been associated with fluoxetine (Coulter and Pillans, 1995; Gram, 1994; Lipinski et al., 1989). These adverse effects may relate to fluoxetine’s selective enhancement of serotonin transmission, which results in the inhibition of dopaminergic neurons (Meltzer et al.,

1979). Consistent with this hypothesis, dopamine depletion is thought to play a central role in the pathophysiology of RLS; dopamine antagonists worsen RLS and dopamine agonist therapy improves RLS (Kaplan and Mason, 1992). In summary, I have presented a patient who developed a dose-dependent, reversible, prominent re-activation of RLS associated with fluoxetine. Clinicians should be aware of this potential interaction when beginning fluoxetine in patients with RLS.

References Coulter, D,M,, Pillans, P.L (1995) Fluoxetine and extrapyramidal side effects. Am. J. Psychiatry, 152: 122– 125. Ekbom, K.A. (1960) Restless legs syndrome. Neurology, 10: 868–873. Gram, L,F. (1994) Fluoxetine. N Engl. J. Med., 331: 1354-1361, Kaplan, B., Mason, N.A, (1992) Levodopa in restless legs syndrome. Ann. Pharmacother., 26: 214–216. Lang, A.E. (1993) Akathisia and the restless legs syndrome. In: Parkinson’s Disease and Movement Disorders. Editors: Jankovich, J., Tolosa, E,, Williams and Wilkins, Baltimore, pp 399-418. Lipinski, J.F., Mallaya, F., Zimmerman, P., Pope, H.G. (1989) Fluoxetine-induced akathisia: Clinical and theoretical implications. J. Clin. Psychiatry, 50: 339–34’2, Meltzer, H.Y., Young, M., Metz, J., et al. (1979) Extrapyramidal side effects and increased serum prolactin following ffuoxetine, a new antidepressant. J. Neural Trans., 45: 165– 175. Milne, LK. (1992) Akathisia associated with carbamazepine therapy. N.. Zld. Med. J., 105: 182–183. O’Sullivan, R.L., Greenberg, D.B. (1993) Hz antagonists, restless legs syndrome, and movement disorders. Psychosomatic, 34: 530–532. Terao, T., Terao, M., Yoshimura, R., Abe, K. (1991) Restless legs syndrome induced by lithium. Biol. Psychiatry, 30: 1167– 1170.