There is an association between iron deficiency anemia and RLS; thus patients should be screened with complete blood count indices and for serum ferritin level. The iron deficit will not be found using normal parameters such as a complete blood count and iron level. A serum ferritin level of <50 is associated with RLS.
Similar to other sleep disorders, non-pharmacological intervention is an impor-tant component of therapy (regular exercise, good sleep hygiene) and includes ed-ucation for avoiding exacerbating factors for RLS and PLMD. The decision for pharmacological intervention should be based on severity of the symptoms, degree of sleep disruption and associated daytime sequalae. For example, even an elevated PLMD index in the absence of arousals or daytime sequalae does not warrant medi-cation. In contrast, for moderate to severe disease or significantly elevated index, the decision to treat is self-evident. Iron supplements should be provided for individuals with low serum ferritin levels. The underlying principle mandating therapy includes
148 J.A. Owens and M.B. Witmans
choosing the medication with the least side effects and the lowest dose to control symptoms. The choices of medications are listed below and adult doses are listed.
The only data reported in children include the use of levodopa or pergolide in seven children with RLS and PLMD with ADHD [55]. Improvement was reported in all seven children without side effects. The longest period of use in this case series was 3 years. Overall, systematic evaluation of these medications for RLS and PLMD in children are lacking.
Dopamine precursors are considered first-line in adults. Side effects include orthostatic hypotension, insomnia, daytime fatigue, and somnolence; nausea, and augmentation may occur. Levodopa with benserazide or carbidopa (Sinemet): 100–
125 mg or 200–250 mg at bedtime and additional doses may be needed. Dopamine agonists are becoming more popular because of the fewer side effects, and less aug-mentation. These are used to treat RLS and PLMD. Their side effects include nausea, orthostatic hypotension, insomnia, and somnolence; also, the potential for tolerance exists.
Most commonly used medications are:
– Pramipexole (Mirapex) 0.125–1.0 mg at bedtime, and pergolide (Permax) 0.1–
0.5 mg at bedtime.
– Benzodiazepines have been used for RLS and PLMD. Caution is advised because this class of medication may worsen obstructive sleep apnea.
Commonly used medications include:
– Clonazepam (Klonopin) 0.5–2.0 mg at bedtime – Temazepam 15–30 mg at bedtime
– Nitrazepam 5–10 mg at bedtime.
Opiates are used in RLS and PLMD, but because of risk of dependency and habituation, these are not considered first line of treatment. Oxycodone (Percodan) 5 mg at bedtime, or propoxyphene (Darvon, Darvocet) 200 mg at bedtime; or codeine 15–60 mg at bedtime.
Anticonvulsants are used for RLS. Most common side effects include daytime somnolence: carbamazepine (Tegretol) 200–400 mg at bedtime or gabapentin (Neu-rontin) 100–400 mg at bedtime are often used.
Clonidine is used for RLS; 0.05–0.2 mg at bedtime; the side effects include hypotension.
These medications, although used clinically, have not been evaluated for children.
Conclusions
Pediatric sleep disorders are common, have significant effects on daytime func-tioning of children and families, and most are amenable to some combination of behavioral management strategies and pharmacological treatment. It is particularly important for the primary care physician to screen for sleep problems in children,
Clinical pharmacology of sleep disturbances in children and adolescents 149
especially in high-risk populations. A detailed history evaluating circumstances re-lated to the sleep problem should be obtained. Addition of pharmacological therapy to non-pharmacological interventions for pediatric sleep disorders for disorders such as insomnia, parasomnias, narcolepsy, RLS or PLMs should be diagnostically driven, and should consider both the best match between the medication type and individual patient, as well as the dosing regimen with the least side effects. Until these medica-tions are systematically studied or newer specific agents are developed for pediatric sleep problems, it is necessary for practitioners looking after children to optimize quality of life and sequalae related to sleep problems, while minimizing potential side effects.
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Clinical Pharmacology of Sleep
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