SSRIs, Periodic Limb Movements of Sleep Linked in Children

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Examine Specific SSRIs, Possible Disease Links

The findings of this study bring up some interesting points, and also highlight areas for additional research. Because periodic limb movements of sleep are usually seen in RLS (a condition that can be particularly difficult for pediatric patients to verbally describe), the objective finding of periodic limb movements of sleep should lead clinicians to obtain a careful history to identify RLS, which can be confused with other phenomena, such as the frequently reported condition of "growing pains" in children. This study leaves it unclear as to whether the periodic limb movements of sleep were related to the SSRI specifically, or to the underlying disorder that necessitated treatment with SSRIs.

Another important point is that periodic limb movements of sleep have recently been suggested to be associated with a higher incidence of cardiovascular disease (Circulation 2011;124:1223-31), which means this finding in children warrants further careful research.

Dr. Brian Murray

Clinical practice is unlikely to change based on Dr. Vendrame and colleagues’ findings, but if periodic limb movements are associated with insomnia clinically, or if they are indeed confirmed to increase cardiovascular risk, other medications may be tried that are less likely to be associated with periodic limb movements of sleep.

The authors did not find a difference between a few specific SSRI medications, but a larger sample size would be required to assess which agents are more likely to induce the condition. The timing of medication administration and dosage also may possibly be altered to minimize the occurrence of periodic limb movements.

Brian Murray, M.D., is director of integrated medical education for the department of medicine at the University of Toronto and associate professor of neurology and sleep medicine at Sunnybrook Health Sciences Center, Toronto.



Children who are treated with selective serotonin reuptake inhibitors have fivefold greater odds of experiencing periodic limb movements of sleep than do those who are not treated with SSRIs, according to findings from a retrospective review of polysomnography data.

Nearly a third (31.7%) of 41 children receiving SSRIs at the time of the study experienced periodic limb movements of sleep, compared with only 7.8% of 982 children not receiving SSRIs (odds ratio, 5.45), Dr. Martina Vendrame of Boston University and her colleagues reported.

Furthermore, the median periodic limb movement index in those receiving SSRIs was significantly higher than the index in those not receiving SSRIs (11.2 vs. 6.5), the investigators said (Pediatr. Neurol. 2011;45:175-7).

Although periodic limb movements of sleep have been reported in adults taking serotonergic antidepressants – with one study showing that 44% of adults receiving fluoxetine experienced the symptoms, and others showing that restless legs syndrome (RLS) is exacerbated in up to 10% of adult patients on SSRIs – the current study is one of few that provide information about periodic limb movements of sleep in children and adolescents.

Study subjects were all children who underwent overnight diagnostic polysomnography between January 2009 and April 2010 at a single center. The studies were conducted for various sleep disturbances such as snoring, pauses in breathing, daytime sleepiness, and gasping or snorting in sleep; none was conducted for reports of RLS or periodic limb movements of sleep.

The patients who received SSRIs included 31 girls and 10 boys who had a median age of 15.4 years. The SSRIs were prescribed for depression and included citalopram or escitalopram in 15 patients, fluoxetine in 14 patients, and sertraline in 12 patients.

"The mechanism by which SSRIs may cause periodic limb movements of sleep is not clear, but serotonin-mediated dopaminergic inhibition may represent the underlying mechanism," the investigators noted.

Although no significant differences in mean periodic limb movements of sleep indices were seen between different SSRIs in this study, it is possible that different doses and timing of administration could result in better control of limb movements, they said, adding that when periodic limb movements of sleep are found, a careful history should be taken to assess whether they are causing sleep disturbance, and also to determine if the child is experiencing RLS.

"If necessary, the use of antidepressants not associated with periodic limb movements of sleep should be considered," they wrote.

Although limited by the use of single-night polysomnography, a small study population, and possibly by referral bias to a tertiary center, the findings suggest that periodic limb movements of sleep may be an important side effect of SSRIs that is frequently overlooked in children.

"Recognition may result in better control of periodic limb movements of sleep and improved quality of life in these patients," they concluded, noting that future investigations should include a multicenter, prospective study using multinight polysomnography, investigation of various SSRIs separately, and evaluation of the role of underlying diseases for which subjects are treated with antidepressants in the development of periodic limb movements of sleep.

No financial disclosure information was available in the report.

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