Practice parameters for the dopaminergic treatment of restless legs syndrome and periodic limb movement disorder

Dopaminergic agents, particularly dopamine agonists, have been used with increasing frequency in the treatment of restless legs syndrome and periodic limb movement disorder. These evidence-based practice parameters are complementary to the Practice Parameters for the Treatment of Restless Legs Syndrome and Periodic Limb Movement Disorder, published in 1999. These practice parameters were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. Recommendations are based on the accompanying comprehensive review of the medical literature regarding the dopaminergic treatment of restless legs syndrome (RLS) and periodic limb movement disorder (PLMD), which was developed by a task force commissioned by the American Academy of Sleep Medicine. The following recommendations serve as a guide to the appropriate use of dopaminergic agents in the treatment of RLS and PLMD. Levodopa with decarboxylase inhibitor, and the dopaminergic agonists pergolide, pramipexole, and ropinirole are effective in the treatment of RLS and PLMD. Other dopamine agonists (talipexole, cabergoline, piribidel, and alpha-dihydroergocryptine) and the dopaminergic agents amantadine and selegiline may be effective in the treatment of RLS and PLMD, but the level of effectiveness of these medications is not currently established. Lastly, no specific recommendations can be made regarding dopaminergic treatment of children or pregnant women with RLS or PLMD.     

Cognitive and Behavioral Anomalies Among Insomnia Patients With Mixed Restless Legs and Periodic Limb Movement Disorder

This study examined whether patients who have periodic limb movement disorder (PLMD), with or without comorbid restless legs syndrome (RLS), display the sleep-disruptive cognitive and behavioral anomalies found among primary insomnia sufferers. Archival data from a Sleep History Questionnaire, home-based polysomnography, and a sleep log were obtained for matched RLS/PLMD, primary insomnia, and noncomplaining volunteer samples. Statistical comparisons showed that the RLS/PLMD and primary insomnia samples differed significantly from the normal sleepers in regard to their propensities for certain sleep disruptive habits, perceived difficulties controlling pre-sleep cognitive activity, and their subjective sleep appraisals. These findings suggest RLS/PLMD patients display many of the cognitive and behavioral anomalies thought to perpetuate primary insomnia. Hence, behavioral interventions may be warranted for RLS/PLMD patients.     

Cognitive and behavioral anomalies among insomnia patients with mixed restless legs and periodic limb movement disorder

This study examined whether patients who have periodic limb movement disorder (PLMD), with or without comorbid restless legs syndrome (RLS), display the sleep-disruptive cognitive and behavioral anomalies found among primary insomnia sufferers. Archival data from a Sleep History Questionnaire, home-based polysomnography, and a sleep log were obtained for matched RLS/PLMD, primary insomnia, and noncomplaining volunteer samples. Statistical comparisons showed that the RLS/PLMD and primary insomnia samples differed significantly from the normal sleepers in regard to their propensities for certain sleep disruptive habits, perceived difficulties controlling pre-sleep cognitive activity, and their subjective sleep appraisals. These findings suggest RLS/PLMD patients display many of the cognitive and behavioral anomalies thought to perpetuate primary insomnia. Hence, behavioral interventions may be warranted for RLS/PLMD patients.     

Practice parameters for the treatment of restless legs syndrome and periodic limb movement disorder. An American Academy of Sleep Medicine Report. Standards of Practice Committee of the American Academy of Sleep Medicine

These are the first clinical guidelines published for the treatment of Restless Legs Syndrome (RLS) and Periodic Limb Movement Disorder (PLMD) providing evidence-based practice parameters. They were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. The guidelines provide recommendations for the practice of sleep medicine in North America regarding the treatment of RLS and PLMD. Recommendations are based on the accompanying comprehensive review of the medical literature regarding treatment of RLS and PLMD which was developed by a task force commissioned by the American Academy of Sleep Medicine. Recommendations are identified as standards, guidelines, or options, based on the strength of evidence from published studies that meet criteria for inclusion. Dopaminergic agents are the best studied and most successful agents for treatment of RLS and PLMD. Specific recommendations are also given for the use of opioid, benzodiazepine, anticonvulsant, and adrenergic medications, and for iron supplementation. In general, pharmacological treatment should be limited to individuals who meet diagnostic criteria and especially who experience insomnia and/or excessive sleepiness that is thought to occur secondary to RLS or PLMD. Individuals treated with medication should be followed by a physician and monitored for clinical response and adverse effects. It would be desirable for future investigations to employ multicenter clinical trials, with expanded numbers of subjects using double-blind, placebo-controlled designs, and an assessment of long-term response, side effects, and impact of treatment on quality of life. Evaluation of special groups such as children, pregnant women, and the elderly is warranted.     

Periodic leg movements during sleep in PLMD and RLS patients with and without pramipexole treatment

Objective

Pharmacological treatment of restless legs syndrome (RLS) patients with pramipexole (PPX) is common and evidence based, whereas the effect of pramipexole on periodic leg movements (PLM) in periodic limb movement disorder (PLMD) patients is unknown. The aim of this study was to investigate the effect of pramipexole on sleep parameters and PLM indices in RLS and in PLMD patients.

Material and methods

Retrospectively, data of two consecutive polysomnographies of 47 patients (20 women, 27 men; mean age 59.8?±?13.6 years; range 23–87 years) with RLS (n?=?29) or PLMD (n?=?18) were analyzed. Of these, 15 patients with RLS and 9 patients with PLMD were treated with 0.18 mg pramipexole directly before the second polysomnographic night.

Results

The PLMS (total PML during sleep) index of PLMD patients was significantly higher (p?=?0.007) in untreated as well in treated patients (p?=?0.007) as compared to RLS. It was significantly reduced (p?<?0.03) in both groups under PPX. In RLS + PPX as well as in PLMD + PPX, light sleep significantly increased and deep sleep significantly decreased. The parameters total sleep time (TST) and sleep efficiency showed no significant changes as compared to the first polysomnographic night.

Conclusion

Results of this retrospective study indicate that a single treatment with 0.18 mg pramipexole leads, on the one hand, to a reduction of PLM indices in sleep both in RLS and in PLMD patients but, on the other hand, to an increase of sleep stages 1 and 2 and to a decrease of deep sleep.     

An update on the dopaminergic treatment of restless legs syndrome and periodic limb movement disorder

This paper reviews evidence from April, 1998 through April 2002 for the dopaminergic treatment of the restless legs syndrome (RLS) and periodic limb movement disorder (PLMD). There has been increased study of dopaminergic agents for the treatment of these conditions since publication of a review paper and practice parameters that covered all types of medical treatment of RLS and PLMD in 1999. For this reason, the Restless Legs Syndrome Task Force and the Standards of Practice Committee decided to update the evidence on dopaminergic treatment of these conditions. This paper reviews the literature on levodopa, dopaminergic agonists (pergolide, pramipexole, ropinirole, talipexole, cabergoline, piribidel, DHEC), and other dopaminergic agents (amantadine, selegiline).     

The treatment of restless legs syndrome and periodic limb movement disorder in adults-an update for 2012: practice parameters with an evidence-based systematic review and meta-analyses: an American Academy of Sleep Medicine Clinical Practice Guideline

A systematic literature review and meta-analyses (where appropriate) were performed to update the previous AASM practice parameters on the treatments, both dopaminergic and other, of RLS and PLMD. A considerable amount of literature has been published since these previous reviews were performed, necessitating an update of the corresponding practice parameters. Therapies with a STANDARD level of recommendation include pramipexole and ropinirole. Therapies with a GUIDELINE level of recommendation include levodopa with dopa decarboxylase inhibitor, opioids, gabapentin enacarbil, and cabergoline (which has additional caveats for use). Therapies with an OPTION level of recommendation include carbamazepine, gabapentin, pregabalin, clonidine, and for patients with low ferritin levels, iron supplementation. The committee recommends a STANDARD AGAINST the use of pergolide because of the risks of heart valve damage. Therapies for RLS secondary to ESRD, neuropathy, and superficial venous insufficiency are discussed. Lastly, therapies for PLMD are reviewed. However, it should be mentioned that because PLMD therapy typically mimics RLS therapy, the primary focus of this review is therapy for idiopathic RLS. CITATION: Aurora RN; Kristo DA; Bista SR; Rowley JA: Zak RS; Casey KR; Lamm CI; Tracy SL; Rosenberg RS. The treatment of restless legs syndrome and periodic limb movement disorder in adults-an update for 2012: practice parameters with an evidence-based systematic review and meta-analyses. SLEEP 2012;35(8):1039-1062.     

Neurotoxic lesions at the ventral mesopontine junction change sleep time and muscle activity during sleep: an animal model of motor disorders in sleep

There is no adequate animal model of restless legs syndrome (RLS) and periodic leg movements disorder (PLMD), disorders affecting 10% of the population. Similarly, there is no model of rapid eye movement (REM) sleep behavior disorder (RBD) that explains its symptoms and its link to Parkinsonism. We previously reported that the motor inhibitory system in the brainstem extends from the medulla to the ventral mesopontine junction (VMPJ). We now examine the effects of damage to the VMPJ in the cat. Based on the lesion sites and the changes in sleep pattern and behavior, we saw three distinct syndromes resulting from such lesions; the rostrolateral, rostromedial and caudal VMPJ syndromes. The change in sleep pattern was dependent on the lesion site, but was not significantly correlated with the number of dopaminergic neurons lost. An increase in wakefulness and a decrease in slow wave sleep (SWS) and REM sleep were seen in the rostrolateral VMPJ-lesioned animals. In contrast, the sleep pattern was not significantly changed in the rostromedial and caudal VMPJ-lesioned animals. All three groups of animals showed a significant increase in periodic and isolated leg movements in SWS and increased tonic muscle activity in REM sleep. Beyond these common symptoms, an increase in phasic motor activity in REM sleep, resembling that seen in human RBD, was found in the caudal VMPJ-lesioned animals. In contrast, the increase in motor activity in SWS in rostral VMPJ-lesioned animals is similar to that seen in human RLS/PLMD patients. The proximity of the VMPJ region to the substantia nigra suggests that the link between RLS/PLMD and Parkinsonism, as well as the progression from RBD to Parkinsonism may be mediated by the spread of damage from the regions identified here into the substantia nigra.     

Exogenous melatonin in periodic limb movement disorder: an open clinical trial and a hypothesis

STUDY OBJECTIVES: The etiology of Periodic Limb Movement Disorder (PLMD) as well as the precise role of melatonin in human physiology remains poorly understood. Inspired by a single case observation we performed the presented study in order to obtain first evidence for the hypothesis that exogenous melatonin would decrease PLM's and thereby improves symptoms of PLMD patients. DESIGN: N/A. SETTING: N/A. PATIENTS/PARTICIPANTS: Nine patients with first time diagnosis of PLMD without RLS were treated over a six-week period with 3 mg melatonin, taken between 10 and 11 p.m. INTERVENTIONS: N/A. RESULTS: Melatonin improved well-being in 7 of the 9 patients. Polysomnography, performed prior and at the end of melatonin treatment, demonstrated a significant reduction of investigated movement parameters, such as PLMs, PLM index, PLMs with arousals and PLM-arousal index. Actigraphy, measured over 14 nights prior and during the last 14 days of melatonin treatment, showed a significant reduction in movement rate and minutes with movements during Time in Bed. CONCLUSIONS: The temporal distribution of PLMs, as well as the coupling of PLMs with the phase position of circadian temperature curve, suggest an involvement of the circadian timing system in the pathophysiology of PLMD. Locomotor activity in animals clearly exhibits a circadian pattern and can be strongly influenced by exogenous melatonin. Results suggest a chronobiotic effect of exogenous melatonin in PLMD. More specifically, we hypothesize that the mode of action of melatonin in the presented PLMD patients might have been an increase of output-amplitude of the circadian timing system, thereby enhancing the circadian rhythmicity of locomotor activity with a reduction of sleep motor activity.     

Periodic leg movements and restless legs syndrome

Study objectives

Periodic leg movements (PLM) are a common phenomenon in several somatic and psychiatric disorders, often related to sleep disorders. We examined the prevalence of PLM, periodic leg movement disorder (PLMD), and restless legs syndrome (RLS) in psychiatric inpatients suffering from severe sleep disturbances and tried to find possible influences of the prescribed medication.

Design, setting and patients

In a retrospective data analysis, we explored the patient’s records in 117 psychiatric inpatients, suffering from comorbidity with severe sleep disturbances.

Measurements and results

We found PLM was positive in 61.5% of our sample, while diagnosing PLMD in 25.6% and RLS in 19.7%. A total of 74% of our RLS patients suffered from PLM. Adding dopaminergic medication or reducing neuroleptic agents improved subjective sleep quality and lowered PLM indices in patients with persistent sleep disturbances. Age-related results showed high PLM scores in patients below 40 years.

Conclusions

PLM occurred in more than 60% of the study group and a PLMD was found in about 25% of our patients. We found PLM indices in our younger patients relatively high in comparison with healthy adults. However, we found no statistically significant influence of the initially prescribed medication – maybe due to polypharmacy. Goal-directed addition of dopaminergic agents or the reduction of neuroleptic drugs results in lower PLM indices and improved subjective sleep quality.     

Moderate to severe periodic limb movement disorder in childhood and adolescence.

The purpose of this study is to review clinical features of children with moderate to severe Periodic Limb Movement Disorder (PLMD). Because of our interest in both Restless Legs Syndrome (RLS) and Attention-Deficit Hyperactivity Disorder (ADHD), many of our patients had one or both of these conditions. We did a retrospective review of 129 children and adolescents who were found to have Periodic Limb Movements in Sleep (PLMS) > 5/hour of sleep. Sixty five had PLMS of 5-10/hour of sleep, 48 had PLMS of 10-25/hour of sleep and 16 had PLMS > 25/hour of sleep. One hundred and seventeen of the original 129 had ADHD. Stimulant medication did not seem to play a role in the production of PLMS. In only 25 of the 129 cases did parents note the presence of PLMS before being specifically asked to look, and even after specific instructions to look, PLMS were not noted by the parents in 39 patients. The sub-group of 16 children and adolescents--6 female, 10 male (average age 11.1 years--range 6-17 years) with moderate to severe PLMS > 25/hour of sleep are described in more detail. Fifteen of the 16 patients had ADHD. Four of the 16 had RLS and 10 of 13 patients for whom a family history was available had a parent with RLS. Two of the 16 patients had their PLMS initially misdiagnosed as seizures. Sleep disturbance was present in all 16 patients and 7 of the 16 had daytime somnolence which resolved with dopaminergic medications. To our knowledge this is the first clinical series of moderate to severe PLMS in children and adolescents to be fully described in the literature.     

Parent-reported periodic limb movement, sleep disordered breathing, bedtime resistance behaviors, and ADHD

The purpose of this study was to compare the relative strength of association between symptoms of attention deficit/hyperactivity disorder (ADHD) with sleep disordered breathing (SDB), periodic limb movement disorder (PLMD), and bedtime resistance behaviors (BRBs). The Pediatric Sleep Questionnaire was completed by parents of 283 children. Scales were derived to indicate risk for specific sleep disorders, then correlated with symptoms of ADHD. Strong independent interrelationships between symptoms of PLMD and symptoms of ADHD emerged, with potential additional contributions by bedtime resistance. These interrelationships remained after controlling for age, SDB, sleepiness, or BRBs. These data suggest ADHD symptoms may be especially related to PLMD but that insufficient sleep duration secondary to bedtime resistance and noncompliance may make an independent contribution.     

Parent-Reported Periodic Limb Movement,Sleep Disordered Breathing,Bedtime Resistance Behaviors,and ADHD

The purpose of this study was to compare the relative strength of association between symptoms of attention deficit/hyperactivity disorder (ADHD) with sleep disordered breathing (SDB), periodic limb movement disorder (PLMD), and bedtime resistance behaviors (BRBs). The Pediatric Sleep Questionnaire was completed by parents of 283 children. Scales were derived to indicate risk for specific sleep disorders, then correlated with symptoms of ADHD. Strong independent interrelationships between symptoms of PLMD and symptoms of ADHD emerged, with potential additional contributions by bedtime resistance. These interrelationships remained after controlling for age, SDB, sleepiness, or BRBs. These data suggest ADHD symptoms may be especially related to PLMD but that insufficient sleep duration secondary to bedtime resistance and noncompliance may make an independent contribution.     

Periodic limb movement disorder of sleep in children

To characterize periodic limb movement disorder (PLMD) in a cohort of prepubertal children we examined sleep-related identifiable differences between children with PLMD and attention-deficit/hyperactivity disorder (ADHD), PLMD alone, and age-matched controls. Children were selected from a chart review of all children referred to a pediatric sleep medicine center and from a community survey of 5-7-year-old-children. Polysomnography (PSG) and parental report data from all children identified as having periodic limb movement index (PLMI) >5 were reviewed and compared with a cohort of age-matched controls. A total of 8.4% of children in the clinic-referred sample, and 11.9% of the children recruited from the community had PLMI >5. Of those, 44.4% were identified as having ADHD. Children with PLMD had significantly lower percentage of rapid eye movement (REM) than control children (P < 0.001). Children in the PLMD/ADHD group had a significantly greater number of arousals associated with PLM (PLMa) than children with PLMD only (P < 0.05). While a relationship between ADHD and PLMD was observed, it was weaker than previous reports (Chervin, R. D. et al. Sleep, 2002; 25: 213; Chervin, R. D. and Archbold, K. H. Sleep, 2001; 24: 313; Picchietti et al. J. Child Neurol., 1999; 13: 588; Picchietti et al. Mov. Disord., 1999; 14: 1000; Picchietti and Walters Sleep, 1999; 22: 297). Children in the PLMD/ADHD group were more likely to have PLMas than were children with PLMD only. We postulate that rather than a direct relationship between ADHD and PLMD, this link may be mediated by the presence of reduced REM sleep and more importantly by the sleep fragmentation associated with PLM-induced arousals.     

Change in periodic limb movement index during treatment of obstructive sleep apnea with continuous positive airway pressure

STUDY OBJECTIVES: The following hypotheses were investigated: 1) severe obstructive sleep apnea (OSA) can mask concurrent periodic limb movement (PLM) disorder (PLMD), which becomes evident or worsens after treatment with continuous positive airway pressure (CPAP); 2) in patients with mild OSA, PLMs are not masked but may be triggered by subclinical hypopneas or respiratory effort-related arousals and improve after CPAP. DESIGN: Retrospective analysis was performed on 2 polysomnographic studies per patient--1 baseline, the second with CPAP titration. The apnea-hypopnea index (AHI) and PLM index (PLMI) under the 2 conditions were statistically analyzed. SETTING: University hospital sleep disorders center. PATIENTS: Patients were selected if they had a baseline AHI of 5 or greater and CPAP titration resulted in reduced AHI. Also, each needed to have either a PLMI of 5 or greater on baseline PSG or during CPAP titration. Patients who started or discontinued a medication that could affect PLMs after the baseline PSG were excluded. INTERVENTIONS: As clinically indicated, CPAP for OSA. MEASUREMENTS AND RESULTS: Eighty-six patients qualified and were divided into 3 groups based on OSA severity. Significant correlations (P < 0.05) were found between AHI and PLMI on the baseline PSG (-0.50), between AHI on baseline PSG and PLMI on CPAP titration (0.49), and between PLMI on baseline PSG and on CPAP titration (-0.21). The increase in PLMI during CPAP titration in patients with severe OSA was statistically significant (P < 0.001). The PLMI decreased with CPAP in 20 of 86 patients, mostly in the mild OSA subgroup. Regression of post-CPAP reduction of AHI and change in PLMI yielded a significant logarithmic relationship (R2 = 0.3042). CONCLUSIONS: Severity of OSA may determine the effect of CPAP on PLMs. The PLMs may increase in moderate to severe OSA due mainly to "unmasking" of underlying PLMD. The PLMs may decrease in mild OSA post-CPAP due to resolution of PLMs associated with respiratory effort-related arousals. This suggests that PLMs may have more than 1 etiology and may be categorized as spontaneous (as in PLMD) and induced (when secondary to respiratory effort-related arousals).     

Cardiac variability and heart-rate increment as a marker of sleep fragmentation in patients with a sleep disorder: a preliminary study

STUDY OBJECTIVES: The ratio between the heart-rate increment to total power spectral density (%VLFI) has been introduced as a sensitive measure of sleep-related breathing disorders (SRBD). Since a complex interaction is present between sleep disorders and occurrence of arousals, we hypothesized that %VLFI and other indexes of heart-rate variability (HRV) measures reflect the degree of sleep fragmentation. METHODS: The high- and low-frequency peaks from spectral analysis (FFT) of R-R intervals, the HRV changes using wavelet transform (WT), the geometric and time domain HRV, and the %VLFI were measured in 336 sleep studies performed in patients with insomnia, SRBD and restless legs syndrome/periodic limb movement disorder (RLS/PLMD). The ability of HRV measures to assess sleep fragmentation was examined by correlation analysis and from the area under the receiver operating characteristic (ROC) curve. RESULTS: The ratio of low frequency to high frequency (LF/HF ratio) at the FFT and WT and the %VLFI were higher in patients with SRBD and RLS/PLMD, compared with patients with insomnia. These measures were related to the arousal (MA) index as well as to the apnea-hypopnea index, oxygen desaturations, and periodic leg movement index (p < .001). The presence of a sleep fragmentation defined as an MA index > 20 was well detected by the %VLFI (ROC area: 0.66 +/- 0.03) and the LF/HF ratio at WT (ROC area: 0.66 +/- 0.03). CONCLUSION: The %VLFI and LF/HF ratio provide indirect measures of sleep fragmentation, suggesting that HRV measures during sleep assess more the associated sleep fragmentation than the presence of a specific sleep disorder.     

Indications for performing polysomnography in the diagnosis and treatment of restless legs syndrome

Summary Restless legs syndrome (RLS) is diagnosed clinically by evaluating the patient's complaints. Diagnostic criteria based on the clinical symptoms were defined by the International Restless Legs Syndrome Study Group. Laboratory and/or neurophysiological assessments can differentiate a primary (idiopathic) RLS from a secondary (associated with an other disease) RLS. Some differential diagnostic and therapeutic issues may, however, require polysomnographic assessment. An investigation in the sleep laboratory should be considered in the following cases: 1) in patients with "atypical" RLS symptoms to support the diagnosis, before pharmacological treatment is begun; 2) in patients on sufficient dopaminergic treatment but still suffering from sleep disturbance, in order to exclude other sleep-related disorders; 3) in patients with mild RLS but marked daytime sleepiness as the main symptom; 4) to support the diagnosis in young patients with severe RLS before dopaminergic treatment is begun or in patients with severe RLS before the start of a treatment with opiates; 5) in patients with RLS and sleep-related respiratory disorders; 6) and finally in patients who are involved in a formal expert's opinion report. Further indications may exist in exceptional cases. A recommendation for performing polysomnography should be always made by a clinician experienced in the diagnosis and treatment of sleep disorders.     

Restless legs syndrome and attention-deficit/hyperactivity disorder: a review of the literature

STUDY OBJECTIVE: To review evidence on the association between restless legs syndrome (RLS) and attention-deficit/hyperactivity disorder (ADHD), to discuss the hypothetical mechanisms underlying this association, and to consider the potential interest for common pharmacologic treatments of RLS and ADHD when co-occurring. METHOD: A PubMed search. RESULTS: In clinical samples, up to 44% of subjects with ADHD have been found to have RLS or RLS symptoms, and up to 26% of subjects with RLS have been found to have ADHD or ADHD symptoms. Several mechanisms may explain this association. Sleep disruption associated with RLS might lead to inattentiveness, moodiness, and paradoxical overactivity. Diurnal manifestations of RLS, such as restlessness and inattention, might mimic ADHD symptoms. Alternatively, RLS might be comorbid with idiopathic ADHD. Subjects with RLS and a subset of subjects with ADHD might share a common dopamine dysfunction. Limited evidence suggests that some dopaminergic agents, such as levodopa/carbidopa, pergolide, and ropinirole, may be effective in children with RLS associated with ADHD symptoms. CONCLUSIONS: Although still limited, evidence from clinical studies demonstrates an association between RLS and ADHD or ADHD symptoms. Further clinical studies using standard criteria and procedures are needed to better estimate the degree of association. Epidemiologic studies are required to assess the relationship between ADHD and RLS symptoms in nonclinical samples. Further investigations should address the mechanisms underlying the relationship between RLS and ADHD. Several dopaminergic agents seem to be promising treatment for RLS associated with ADHD symptoms. To date, however, the absence of randomized and blinded controlled studies does not allow evidence-based recommendations.     

Preclinical evidence for GABAB agonists as a pharmacotherapy for cocaine addiction

A variety of studies indicate that GABA(B) receptor agonists may be useful in the treatment of addictive disorders. This brief review summarizes self-administration studies in rats which show that baclofen and other GABA(B) agonists may have specific effects on the reinforcing effects of cocaine. Preliminary clinical data with baclofen have also been encouraging. The obstacles and issues related to the use of GABA drugs in addiction therapy are briefly addressed.     

Some children with growing pains may actually have restless legs syndrome

STUDY OBJECTIVES: Growing pains may be an important clue to the diagnosis of childhood restless legs syndrome (RLS). However, there are no previous studies to determine whether a subpopulation of children with growing pains meet the diagnostic criteria for RLS. The purpose of this study is to determine if some children with growing pains meet diagnostic criteria for RLS and to compare the polysomnographic characteristics of these children to controls. DESIGN/PARTICIPANTS/MEASUREMENTS: Eleven children from a pediatric neurology clinic with an emphasis on attention-deficit/hyperactivity disorder (ADHD) and with a diagnosis of growing pains were referred. They were interviewed with the parent to determine if their symptoms of growing pains met criteria for definite RLS. Those who met clinical criteria for RLS underwent polysomnography, and the results of their polysomnographic studies were compared to those of a control group (10 children, mean age 9.7 years). SETTING: Academic medical center. RESULTS: Ten (mean age 10.4 years) of the 11 children with growing pains met clinical criteria for RLS. In 4 of 8 families of these 10 children, 1 parent had RLS. Six of the 10 children had ADHD. There were no differences in the polysomnographic findings between the growing-pain and control groups, and none of the children with RLS had what is considered to be a clinically significant number of periodic limb movements of sleep. There were no differences in the polysomnographic findings between the "growing-pain ADHD" and "growing-pain non-ADHD" subgroups. The growing pains were severe enough for the patients and family to ask for treatment in 4 cases, and carbidopa/levodopa was utilized. CONCLUSIONS: Some children diagnosed with growing pains meet diagnostic criteria for RLS, and a family history of RLS is common in these children. In some cases symptoms are severe enough to warrant treatment.