BACKGROUND: Lower-sodium oxybate (LXB) is an oxybate medication with the same active moiety as sodium oxybate (SXB) and a unique composition of cations, resulting in 92% less sodium. LXB was shown to improve cataplexy and excessive daytime sleepiness in people with narcolepsy in a placebo-controlled, double-blind, randomized withdrawal study (NCT03030599). Additional analyses of data from this study were conducted to explore the effects of LXB on cataplexy, including the clinical course and feasibility of transition from other anticataplectics to LXB monotherapy. OBJECTIVE: The aim of these analyses was to evaluate cataplexy frequency during initiation/optimization of LXB and taper/discontinuation of prior antidepressant/anticataplectic medications. METHODS: Eligible participants (adults aged 18-70 years with narcolepsy with cataplexy) entered the study taking SXB only (group A), SXB + other anticataplectics (group B), or anticataplectic medication other than SXB (group C), or were cataplexy-treatment naive (group D). LXB was initiated/optimized during a 12-week, open-label, optimized treatment and titration period (OLOTTP). Other anticataplectics were tapered/discontinued during weeks 3-10 of OLOTTP. A 2-week stable-dose period (SDP; during which participants took a stable dose of open-label LXB) and 2-week double-blind randomized withdrawal period (during which participants were randomized to continue LXB treatment or switch to placebo) followed OLOTTP. Treatment-emergent adverse events (TEAEs) were recorded throughout the duration of the study. RESULTS: At the beginning of OLOTTP, median weekly cataplexy attacks were lower in participants taking SXB at study entry (SXB only [2.00]; SXB + other anticataplectics [0.58]) versus participants who were taking other anticataplectics (3.50) or were anticataplectic naive (5.83). Median weekly cataplexy attacks decreased during weeks 1-2 of OLOTTP in all groups. Increased cataplexy frequency was observed in participants tapering/discontinuing other anticataplectics during weeks 3-10 and was more prominent in participants taking other anticataplectics alone compared with those taking SXB plus other anticataplectics. Cataplexy frequency decreased throughout initiation/optimization in anticataplectic-naive participants. Median number of cataplexy-free days/week at the end of SDP (study week 14) was similar in all groups (6.0, 6.1, 6.0, and 6.2 in groups A, B, C, and D, respectively). During OLOTTP and SDP, TEAEs of worsening cataplexy were reported in 0%, 47.8%, 16.7%, and 2.2% of participants in groups A, B, C, and D, respectively; most TEAEs of worsening cataplexy were reported during tapering/discontinuation of other anticataplectics. CONCLUSIONS: LXB monotherapy was effective in reducing cataplexy and increasing cataplexy-free days. These results illustrate the feasibility of switching from SXB to LXB while tapering/discontinuing other anticataplectics. TRIAL REGISTRATION: A Study of the Efficacy and Safety of JZP-258 in Subjects With Narcolepsy With Cataplexy; https://clinicaltrials.gov/ct2/show/NCT03030599 ; clinicaltrials.gov identifier: NCT03030599.

• MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• kataplexie * farmakoterapie   MeSH
• lidé MeSH
• narkolepsie * chemicky indukované   farmakoterapie   MeSH
• oxybát sodný * škodlivé účinky   MeSH
• poruchy nadměrné spavosti * farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Idiopathic hypersomnia is a central hypersomnolence disorder mainly characterised by excessive daytime sleepiness, with prolonged night-time sleep and pronounced sleep inertia. Until August, 2021, no medication had regulatory approval for the treatment of idiopathic hypersomnia. This study aimed to evaluate the safety and efficacy of lower-sodium oxybate in idiopathic hypersomnia. METHODS: This was a phase 3, multicentre (50 specialist sleep centres; six EU countries and the USA), placebo-controlled, double-blind, randomised withdrawal study. Participants (aged 18-75 years) with idiopathic hypersomnia (meeting criteria from the International Classification of Sleep Disorders, 2nd or 3rd editions) began lower-sodium oxybate treatment (oral solution once or twice nightly) in an open-label titration and optimisation period (10-14 weeks), followed by a 2-week, open-label, stable-dose period. After these open-label periods, participants were randomised (1:1) by means of an interactive web recognition system, stratified by participants' baseline medication use, to either placebo or lower-sodium oxybate (individually optimised dose; range 2·5-9·0 g/night) during a 2-week, double-blind, randomised withdrawal period. To maintain masking of treatment assignment, placebo and lower-sodium oxybate oral solutions were matched in volume, appearance, and taste. During the double-blind, randomised withdrawal period, participants and investigators were unaware of treatment assignments. The primary efficacy endpoint was change in Epworth Sleepiness Scale (ESS) score from the end of the stable-dose period to the end of the double-blind, randomised withdrawal period, which was assessed in the modified intention-to-treat population (defined as all participants who were randomly assigned, took at least one dose of study medication during the double blind, randomised withdrawal period, and had at least one set of post-randomisation assessments for the primary or key secondary endpoints). Adverse events were assessed in the safety population (defined as all participants who took at least one dose of study medication). This study is registered at ClinicalTrials.gov, NCT03533114, and at EU Clinical Trials, 2018-001311-79, and is complete. FINDINGS: Between Nov 27, 2018, and March 6, 2020, 154 participants were enrolled and comprised the safety population. ESS scores decreased from a mean of 15·7 (SD 3·8) at baseline to 6·1 (4·0) by the end of the stable-dose period. After the open-label periods, 115 participants were randomly assigned either placebo (n=59) or lower-sodium oxybate (n=56) and comprised the modified intention-to-treat population. During the double-blind, randomised withdrawal period, ESS scores increased (worsened) in participants randomly assigned to placebo but remained stable in those assigned to lower-sodium oxybate (least squares mean difference -6·5; 95% CI -8·0 to -5·0; p<0·0001). Treatment-emergent adverse events included nausea (34 [22%] of 154), headache (27 [18%] of 154), dizziness (19 [12%] of 154), anxiety (17 [11%] 154), and vomiting (17 [11%] 154). No deaths were reported during the study. INTERPRETATION: Lower-sodium oxybate treatment resulted in a clinically meaningful improvement in idiopathic hypersomnia symptoms, with an overall safety profile consistent with that reported for narcolepsy. Lower-sodium oxybate was approved in August, 2021, by the US Food and Drug Administration for the treatment of idiopathic hypersomnia in adults. FUNDING: Jazz Pharmaceuticals.

• MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• idiopatická hypersomnie * farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• oxybát sodný * škodlivé účinky   MeSH
• poruchy nadměrné spavosti * chemicky indukované   farmakoterapie   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• komentáře MeSH
• práce podpořená grantem MeSH

STUDY OBJECTIVES: Evaluate efficacy and safety of lower-sodium oxybate (LXB), a novel oxybate medication with 92% less sodium than sodium oxybate (SXB). METHODS: Adults aged 18-70 years with narcolepsy with cataplexy were eligible. The study included a ≤30-day screening period; a 12-week, open-label, optimized treatment and titration period to transition to LXB from previous medications for the treatment of cataplexy; a 2-week stable-dose period (SDP); a 2-week, double-blind, randomized withdrawal period (DBRWP); and a 2-week safety follow-up. During DBRWP, participants were randomized 1:1 to placebo or to continue LXB treatment. RESULTS: Efficacy was assessed in 134 participants who received randomized treatment, and safety was assessed in all enrolled participants (N = 201). Statistically significant worsening of symptoms was observed in participants randomized to placebo, with median (first quartile [Q1], third quartile [Q3]) change in weekly number of cataplexy attacks from SDP to DBRWP (primary efficacy endpoint) in the placebo group of 2.35 (0.00, 11.61) versus 0.00 (-0.49, 1.75) in the LXB group (p < 0.0001; mean [standard deviation, SD] change: 11.46 [24.751] vs 0.12 [5.772]), and median (Q1, Q3) change in Epworth Sleepiness Scale score (key secondary efficacy endpoint) of 2.0 (0.0, 5.0) in the placebo group versus 0.0 (-1.0, 1.0) in the LXB group (p < 0.0001; mean [SD] change: 3.0 [4.68] vs 0.0 [2.90]). The most common treatment-emergent adverse events with LXB were headache (20.4%), nausea (12.9%), and dizziness (10.4%). CONCLUSIONS: Efficacy of LXB for the treatment of cataplexy and excessive daytime sleepiness was demonstrated. The safety profile of LXB was consistent with SXB. CLINICAL TRIAL REGISTRATION: NCT03030599.

• MeSH
• dospělí MeSH
• draslík MeSH
• dvojitá slepá metoda MeSH
• hořčík MeSH
• kataplexie * farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• narkolepsie * farmakoterapie   MeSH
• oxybát sodný * škodlivé účinky   terapeutické užití   MeSH
• senioři MeSH
• sodík MeSH
• vápník MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Onemocnění spojená s narušením nebo zkrácením spánku a s nadměrnou denní spavostí svými zdravotními důsledky významně snižují kvalitu života. Narůstající výskyt nespavosti vede k nadměrnému a neracionálnímu užívání hypnotik namísto nefarmakologických postupů, které jsou léčbou první volby. Farmakoterapie je indikována u akutní insomnie, u chronické insomnie má její krátkodobé použití podporovat režimová opatření a psychoterapeutické postupy. V léčbě insomnie se upřednostňují nebenzodiazepinová hypnotika. Dalšími používanými léčivy jsou benzodiazepiny, antidepresiva a melatonin. Častým neurologickým onemocněním je syndrom neklidných nohou, který může způsobovat chronickou nespavost a vyžaduje specifickou farmakoterapii (dopaminergní léky, ligandy kalciových kanálů, opioidy). Vzácnými chorobami, obvykle s potřebou celoživotní léčby, jsou centrální hypersomnie (narkolepsie a idiopatická hypersomnie). V této indikaci se užívají stimulancia a k potlačení projevů kataplexie antidepresiva.

Disorders associated with fragmentation or shortening of sleep and/or with excessive daytime sleepiness may have a serious health consequences, and significantly decrease quality of life. The growing prevalence of insomnia leads to frequent and irrational use of hypnotics instead of nonpharmacologic approaches which are considered as a first line treatment. Pharmacotherapy is indicated in acute insomnia. In chronic insomnia, the short‑term drug administration should supplement behavioral, and psychotherapeutic methods. Nonbenzodiazepine hypnotics are preferred drugs for treatment of insomnia. Benzodiazepines, antidepressants and melatonin are used as well. Restless leg syndrome is a common neurological disease which can cause chronic insomnia and requires specific pharmacotherapy (dopaminergic drugs, calcium channel ligands, opioids). Central hypersomnias (narcolepsy and idiopathic hypersomnia) are rare disorders usually necessitating life‑long therapy. Stimulants and antidepressants are used in central hypersomnias to improve vigilance and supress cataplexy, respectively.

• MeSH
• agonisté dopaminu škodlivé účinky   terapeutické užití   MeSH
• antidepresiva škodlivé účinky   terapeutické užití   MeSH
• benzhydrylové sloučeniny škodlivé účinky   terapeutické užití   MeSH
• benzodiazepiny škodlivé účinky   terapeutické užití   MeSH
• hypnotika a sedativa terapeutické užití   MeSH
• levodopa škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• melatoninové receptory agonisté   terapeutické užití   MeSH
• modafinil MeSH
• narkolepsie farmakoterapie   MeSH
• oxybát sodný škodlivé účinky   terapeutické užití   MeSH
• poruchy iniciace a udržování spánku * diagnóza   farmakoterapie   patofyziologie   MeSH
• poruchy nadměrné spavosti * diagnóza   farmakoterapie   patofyziologie   MeSH
• psychotropní léky škodlivé účinky   terapeutické užití   MeSH
• receptory GABA-A - agonisté terapeutické užití   MeSH
• selektivní inhibitory zpětného vychytávání serotoninu škodlivé účinky   terapeutické užití   MeSH
• syndrom neklidných nohou * diagnóza   farmakoterapie   patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Termín taneční nebo klubové drogy odkazuje především na setting, v němž jsou drogy užívány, tj. prostředí tanečních akcí. Podáváme přehled hlavních příznaků akutní intoxikace, dopadů dlouhodobého užívání a využití vybraných „tanečních drog" - MDMA (3,4-metylendioxy-metamfetamin), ketaminu a kyseliny gama-hydroxymáselné (GHB) - v léčbě jiných závislostí. Na trhu se objevují stále nové psychotropní látky, na trendy na drogové scéně musí česká legislativa pružně reagovat.

The term “club drugs” or “dance drugs” generally refers to the setting in which the drugs are used, i.e. club environment or dance events. The article provides an overview of the main symptoms of acute intoxication, the effects of long-term use, and the utilisation of some “dance drugs”, including MDMA (3,4-methylenedioxymethamphetamine), ketamine, and gamma-hydroxybutyric acid (GHB) in the treatment of other addictions. As new psychotropic substances continue to emerge onto the market, the Czech legislation needs to respond flexibly to the latest trends on the drug scene.

• Klíčová slova
• léčba, extáze, kyselina gama-hydroxymáselná,
• MeSH
• financování organizované MeSH
• ketamin aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• N-methyl-3,4-methylendioxyamfetamin aplikace a dávkování   škodlivé účinky   MeSH
• nové syntetické drogy škodlivé účinky   MeSH
• oxybát sodný aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• poruchy spojené s užíváním psychoaktivních látek MeSH
• zakázané drogy škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH