naloxone and Disorders-of-Excessive-Somnolence

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.. To asses the effects of opioids compared to placebo treatment for restless legs syndrome in adults.. 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.. Randomised controlled clinical trials of opioid treatment in adults with idiopathic RLS.. 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.. 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.. 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).

Topics: Analgesics, Opioid; Disorders of Excessive Somnolence; Humans; Naloxone; Oxycodone; Randomized Controlled Trials as Topic; Restless Legs Syndrome

Opioids are a potential new treatment for severe restless legs syndrome. We investigated the efficacy and safety of a fixed-dose combination of prolonged release oxycodone-naloxone for patients with severe restless legs syndrome inadequately controlled by previous, mainly dopaminergic, treatment.. This multicentre study consisted of a 12-week randomised, double-blind, placebo-controlled trial and 40-week open-label extension phase done at 55 sites in Austria, Germany, Spain, and Sweden. Patients had symptoms for at least 6 months and an International RLS Study Group severity rating scale sum score of at least 15; patients with severe chronic obstructive pulmonary disease or a history of sleep apnoea syndrome were excluded. Patients were randomly assigned (1:1) to either study drug or matched placebo with a validated interactive response technology system in block sizes of four. Study drug was oxycodone 5·0 mg, naloxone 2·5 mg, twice per day, which was up-titrated according to investigator's opinion to a maximum of oxycodone 40 mg, naloxone 20 mg, twice per day; in the extension, all patients started on oxycodone 5·0 mg, naloxone 2·5 mg, twice per day, which was up-titrated to a maximum of oxycodone 40 mg, naloxone 20 mg, twice per day. The primary outcome was mean change in severity of symptoms according to the International RLS Study Group severity rating scale sum score at 12 weeks. This study is registered with ClinicalTrials.gov (number NCT01112644) and with EudraCT (number 2009-011107-23).. We screened 495 patients, of whom 306 were randomly assigned and 276 included in the primary analysis (132 to prolonged release oxycodone-naloxone vs 144 to placebo). 197 patients participated in the open-label extension. Mean International RLS Study Group rating scale sum score at randomisation was 31·6 (SD 4·5); mean change after 12 weeks was -16·5 (SD 11·3) in the prolonged release oxycodone-naloxone group and -9·4 (SD 10·9) in the placebo group (mean difference between groups at 12 weeks 8·15, 95% CI 5·46-10·85; p<0·0001). After the extension phase, mean sum score was 9·7 (SD 7·8). Treatment-related adverse events occurred in 109 of 150 (73%) patients in the prolonged release oxycodone-naloxone group and 66 of 154 (43%) in the placebo group during the double-blind phase; during the extension phase, 112 of 197 (57%) had treatment-related adverse events. Five of 306 (2%) patients had serious treatment-related adverse events when taking prolonged release oxycodone-naloxone (vomiting with concurrent duodenal ulcer, constipation, subileus, ileus, acute flank pain).. Prolonged release oxycodone-naloxone was efficacious for short-term treatment of patients with severe restless legs syndrome inadequately controlled with previous treatment and the safety profile was as expected. Our study also provides evidence of open-label long-term efficacy of this treatment. Opioids can be used to treat patients with severe restless legs syndrome who have had no benefit with first-line drugs.. Mundipharma Research.

Topics: Aged; Delayed-Action Preparations; Disorders of Excessive Somnolence; Dopamine Agonists; Double-Blind Method; Female; Flank Pain; Gastrointestinal Diseases; Humans; Male; Middle Aged; Naloxone; Oxycodone; Patient Selection; Quality of Life; Restless Legs Syndrome; Salvage Therapy; Severity of Illness Index; Sleep; Treatment Outcome

Topics: Accidents, Home; Analgesics, Opioid; Biological Availability; Buprenorphine; Disorders of Excessive Somnolence; Humans; Infant; Male; Naloxone; Narcotic Antagonists; Neurotoxicity Syndromes; Respiratory Insufficiency; Treatment Outcome

A simple blind study with small doses of naloxone (0.8-1.6 mg i.v.) was carried out in 11 patients with hypersomnia with sleep apnoea (HSA). The effect was studied by diurnal polysomnography. It was found that the administration of naloxone was followed by significant prolongation of wakefulness and by significant shortening of the total duration of the second stage of NREM sleep. The duration of the apnoeic episodes was also significantly shortened after naloxone, although their number did not alter. Increased activity of the endorphinergic system (which naloxone inhibits by receptor competition) evidently plays a role in the pathophysiology of HSA.

Topics: Adult; Disorders of Excessive Somnolence; Female; Humans; Male; Middle Aged; Naloxone; Single-Blind Method; Sleep Apnea Syndromes; Sleep Wake Disorders; Sleep, REM