Benzodiazepines for restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) is a common disease affecting about 5% to 15% of the population. Symptoms of RLS can be severe in a minority of and can have a major impact on sleep, mostly sleep initiation, and quality of life. Benzodiazepines are drugs that can induce and maintain sleep and, hence, intuitively are thought to be beneficial to people with RLS. Altough benzodiazepines, particularly clonazepam, are used to treat RLS symptoms, a systematic review done by the American Academy of Sleep Medicine stated that benzodiazepines should not be used as a first-line treatment, although could be used as a coadjuvant therapy. OBJECTIVES: To evaluate the efficacy and safety of benzodiazepine compared to placebo or other treatment for idiopathic RLS, including unconfounded trials comparing benzodiazepines versus open control. SEARCH METHODS: In March 2016 we searched CENTRAL, MEDLINE, Embase and LILACS We checked the references of each study and contacted study authors to identify any additional studies. We considered studies published in any language. SELECTION CRITERIA: Randomised clinical trials of benzodiazepine treatment in idiopathic RLS. DATA COLLECTION AND ANALYSIS: We did not perform data collection and analysis, since we did not include any studies, MAIN RESULTS: We did not identify any studies that met the inclusion criteria of the review. Two cross-over studies are awaiting classification because the cross-over trials did not give data at the end of the first cross-over period. AUTHORS' CONCLUSIONS: The effectiveness of benzodiazepines for RLS treatment is currently unknown.

Opioids for restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) is a distressing and common neurological disorder that may have a huge impact in the quality of life of those with frequent and intense symptoms. Patients complain of unpleasant sensations in the legs, at or before bedtime, and feel an urge to move the legs, which improves with movement, such as walking. Symptoms start with the patient at rest (e.g. sitting or lying down), and follow a circadian pattern, increasing during the evening or at night. Many pharmacological intervention are available for RLS, including drugs used to treat Parkinson's disease (L-Dopa and dopaminergic agonists), epilepsy (anticonvulsants), anxiety (benzodiazepines), and pain (opioids). Dopaminergic drugs are those most frequently used for treatment of RLS, but some patients do not respond effectively and require other medication. Opioids, a class of medications used to treat severe pain, seem to be effective in treating RLS symptoms, and are recommended for patients with severe symptoms, because RLS and pain appear to share the same mechanism in the central nervous system. All available drugs are associated to some degree with side effects, which can impede treatment. Opioids are associated with adverse events such as constipation, tolerance, and dependence. This justifies the conduct of a systematic review to ascertain whether opioids are safe and effective for treatment of RLS. OBJECTIVES: To asses the effects of opioids compared to placebo treatment for restless legs syndrome in adults. SEARCH METHODS: We searched the Cochrane Central Register of Controlled trials, CENTRAL 2016, issue 4 and MEDLINE, EMBASE, and LILACS up to April 2016, using a search strategy adapted by Cochraneto identify randomised clinical trials. We checked the references of each study and established personal communication with other authors to identify any additional studies. We considered publications in all languages. SELECTION CRITERIA: Randomised controlled clinical trials of opioid treatment in adults with idiopathic RLS. DATA COLLECTION AND ANALYSIS: Two review authors independently screened articles, independently extracted data into a standard form, and assessed for risk of bias. If necessary, they discussed discrepancies with a third researcher to resolve any doubts. MAIN RESULTS: We included one randomised clinical trial (N = 304 randomised; 204 completed; 276 analysed) that evaluated opioids (prolonged release oxycodone/naloxone) versus placebo. After 12 weeks, RSL symptoms had improved more in the drug group than in the placebo group (using the IRLSSS: MD -7.0; 95% CI -9.69 to -4.31 and the CGI: MD -1.11; 95% CI -1.49 to -0.73). More patients in the drug group than in the placebo group were drug responders (using the IRLSSS: RR 1.82; 95% CI 1.37 to 2.42 and the CGI: RR1.92; 95% ICI 1.49 to 2.48). The proportion of remitters was greater in the drug group than in the placebo group (using the IRLSSS: RR 2.14; 95% CI 1.45 to 3.16). Quality of life scores also improved more in the drug group than in the placebo group (MD -0.73; 95% CI -1.1 to -0.36). Quality of sleep was improved more in the drug group measured by sleep adequacy (MD -0.74; 95% CI -1.15 to -0.33), and sleep quantity (MD 0.89; 95% CI 0.52 to 1.26).There was no difference between groups for daytime somnolence, trouble staying awake during the day, or naps during the day. More adverse events were reported in the drug group (RR 1.22; 95% CI 1.07 to 1.39). The major adverse events were gastrointestinal problems, fatigue, and headache. AUTHORS' CONCLUSIONS: Opioids seem to be effective for treating RLS symptoms, but there are no definitive data regarding the important problem of safety. This conclusion is based on only one study with a high dropout rate (moderate quality evidence).

Pharmacological treatment for Kleine-Levin syndrome.

BACKGROUND: This is an updated version of the original Cochrane review, published in 2009, Issue 2.Kleine-Levin syndrome (KLS) is a rare disorder that mainly affects adolescent men. It is characterised by recurrent episodes of hypersomnia, usually accompanied by hyperphagia, cognitive and mood disturbances, abnormal behaviour, such as hypersexuality, and signs of dysautonomia.In 1990, the diagnostic criteria for Kleine-Levin syndrome were modified in the International Classification of Sleep Disorders, where KLS was defined as a syndrome comprised of recurring episodes of undue sleepiness lasting some days, which may or may not be associated with hyperphagia and abnormal behaviour. According to the International Classification of Sleepiness Disorders, 3rd version (ICSD-3), revised in 2014, the Kleine-Levin syndrome is a disorder characterized by recurrent episodes of hypersomnia that last from two days to four weeks, with at least annual recurrence, and hyperphagia (rapid consumption of a large amount of food), usually with onset in early adolescence in males but occasionally in later life and in women. A monosymptomatic form of the disorder with hypersomnia only can occur without binge eating or hypersexuality.The cause of Kleine-Levin syndrome remains unknown, and several treatment strategies have been used. Some medications have been reported to provide benefit in the treatment of patients with KLS, but because of the rarity of the condition, no long-term follow-up therapies have yet been described. OBJECTIVES: This review aimed to evaluate:1. whether pharmacological treatment for Kleine Levin syndrome was effective and safe.2. which drug or category of drugs was effective and safe. SEARCH METHODS: For the latest update, we searched the following sources: the Cochrane Epilepsy Group Specialized Register (7 April 2016); the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online CRSO (7 April 2016); MEDLINE (1946 to April 2016); LILACS (7 April 2016); ClinicalTrials.gov (7 April 2016); WHO International Clinical Trials Registry Platform ICTRP (7 April 2016); reference lists of sleep medicine textbooks; review articles and reference lists of articles identified by the search strategies. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-randomised controlled trials looking at pharmacological interventions for Kleine-Levin syndrome were eligible. We had planned to include both parallel-group and cross-over studies. DATA COLLECTION AND ANALYSIS: Two review authors (MMO and CC) had planned to extract the data reported in the original articles. MAIN RESULTS: No studies met the inclusion criteria for this systematic review. AUTHORS' CONCLUSIONS: Therapeutic trials of pharmacological treatment for Kleine-Levin syndrome with a double-blind, placebo-controlled design are needed.