Co-Occurring Akathisia and Restless Legs Syndrome Likely Induced By Quetiapine

To the Editor: Atyical neuroleptics commonly cause akathisia, a distressing feeling of generalized restlessness. They have also been rarely reported to cause restless legs syndrome, which has overlapping clinical characteristics with akathisia but is distinguished by dysethesias specifically in the legs, with an irresistible urge to move them. We describe the first reported case of co-occurring RLS and akathishia related to use of the atypical neuroleptic quetiapine.

Case Report

A 44-year-old male with bipolar I disorder was admitted to a psychiatric hospital for worsening depressive symptoms and auditory hallucinations. The patient had previously tried ziprasidone, divalproex, sertraline, and citalopram with minimal improvement. He was eventually started on quetiapine, titrated to 300 mg at bedtime. After several weeks, he reported no medication side effects, but also had no improvement in mood or hallucinations. The quetiapine dose was thus increased to 600 mg, after which he reported improved mood and fewer hallucinations. The night after dose increase, however, he experienced an intense, uncomfortable sensation of tightness in his legs, feeling as though he needed to draw his legs to his chest. This feeling was only relieved by walking or stretching, causing the patient to wake periodically throughout the night. During this time, he also developed a generalized feeling of internal restlessness that occurred during the day and made him feel as though he needed to keep moving. He found this daytime feeling troublesome, but not severe enough to interfere with his daily activities.

On detailed symptom questioning, the nighttime symptoms were noted to be much more severe and feel qualitatively distinct from his daytime symptoms. The night symptoms were characterized by a specific need to move his legs to relieve dysesthesias, rather than the generalized internal restlessness that characterized his daytime symptoms. This symptom presentation is consistent with severe RLS in the background of a more mild case of akathisia.

Because of the side effects, the patient eventually stopped taking quetiapine, and within 3 days of stopping, his akathisia and RLS symptoms completely resolved. Within weeks, however, his psychiatric symptoms worsened and he returned to the hospital. The patient was then started on risperidone 3 mg and sertraline 100 mg daily. On this regimen, he did not experience RLS or akathisia symptoms, and reported significant improvement in mood and hallucinations. The patient was interviewed again several months after discharge home, and reported that he never again experienced the akathisia or RLS symptoms.

Of note, other possible underlying RLS factors were investigated at the last hospital admission. Comprehensive electrolyte panel, BUN and creatinine, iron and ferritin levels, thyroid profile, and glucose levels were all normal. No unusual motor tics or psychomotor agitation were observed on exam.

Discussion

Restless legs syndrome (RLS) is a neurological condition characterized by dysethesias in the legs and the irresistible urge to move them. It can, at first glance, appear similar to akathisia, a syndrome of more general internal restlessness that can occur at any time during the day or night. RLS symptoms, in contrast, are characterized by occurring at night, and involve specific dysethisias in the legs that are relieved by walking.

Neuroleptic-induced akathisia is a common side effect, occurring in over 10% of patients.¹ The prevalence of neuroleptic-induced RLS, on the other hand, is less certain,² with only a few case reports suggesting association with quetiapine.^3–5 Considering the overlapping clinical presentations of these two conditions (for example, excessive feelings of needing to walk around), it is quite possible that neuroleptic-induced RLS is underdiagnosed and misattributed to akathisia. For those reporting difficulty sleeping while taking neuroleptics, it may be useful to ask specifically about symptoms of RLS, even in a patient also describing symptoms more typical of akathisia.