Treatment Of Excessive Daytime Sleepiness Research Articles

Pharmacotherapy of Narcolepsy: Focus on Sodium Oxybate

Narcolepsy is a complex disease with multiple symptoms that include excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. Pharmacologic management of patients with narcolepsy is based on treating these symptoms. Sodium oxybate, a neurotransmitter product of γ-amino butyric acid (GABA), is a Schedule III controlled substance in the US, approved for the treatment of excessive daytime sleepiness (EDS), and cataplexy in patients with narcolepsy. The purpose of this review is to summarize the current knowledge about treatment of narcolepsy with sodium oxybate and to familiarize readers with the safety and efficacy of sodium oxybate, thus enabling clinicians to optimize their management of narcolepsy. A review of the pharmacokinetics, pharmacodynamics, efficacy in different symptoms of narcolepsy, adverse effects, tolerability, and dosing of sodium oxybate is presented. Sodium oxybate administered as an oral solution has a rapid onset of effect, a short duration of action, and nearly complete metabolism with negligible unchanged γ-hydroxybutyrate (GHB) appearing in the urine. There is mounting evidence suggesting that GHB may function as an endogenous neuromodulator/neurotransmitter. The mechanism by which sodium oxybate has a therapeutic effect in narcolepsy is unclear. The efficacy of oral sodium oxybate on the treatment of narcolepsy was evaluated in two randomized, double-blind, placebo- controlled, multicenter, US and International trials. Treatment of patients with narcolepsy-cataplexy with sodium oxybate leads to reduction in the frequency of cataplexy attacks in a dose-related manner, improved EDS, increased level of alertness and ability to concentrate. The major problem with sodium oxybate remains in its potential for non-medical use to elicit altered states of consciousness; however, abuse and misuse of sodium oxybate has been rare over the 7 years since its introduction in the market. Other issues revolve around twice nightly dosing, and salty taste. The most commonly reported adverse events associated with the use of sodium oxybate and occurring with at least 5% greater frequency than seen in placebo-treated patients were dizziness, headache, nausea, pain, night terrors, enuresis, confusion, infection, vomiting, and urinary incontinence. In conclusion, sodium oxybate significantly improves all symptoms in patients with narcolepsy and is well tolerated.

A safety trial of sodium oxybate in patients with obstructive sleep apnea: Acute effects on sleep-disordered breathing

Objective Sodium oxybate (SXB) is an approved drug for the treatment of excessive daytime sleepiness (EDS) and cataplexy in narcolepsy. Obstructive sleep apnea syndrome (OSAS) is a condition that frequently co-occurs with narcolepsy. Given the known central nervous system (CNS) depressant effects of SXB, this study aimed to examine its effects on sleep-disordered breathing (SDB) and sleep architecture in patients with OSAS. Methods Sixty patients with a history of mild to moderate OSAS (apnea-hypopnea index [AHI] ⩾ 10 and ⩽40, mean oxygen saturation [SaO 2] ⩾ 75%) received one of four treatments of the following: (1) 9 g SXB, (2) 9 g SXB/modafinil 200 mg, (3) zolpidem 10 mg, and (4) placebo (PBO) in a randomized, crossover design on four consecutive nights followed by overnight polysomnography. Results Forty-two patients (70%) completed the study. The mean change from baseline in AHI and mean SaO 2 was not significantly different among groups following treatment. Central apneas in patients treated with SXB increased, and clinically significant oxygen desaturations were seen in three patients with SXB treatment. The most common treatment related adverse events were headache and nausea. Conclusion These results suggest that nighttime administration of 9 g SXB in patients with mild to moderate OSAS does not negatively impact SDB, as measured by mean change from baseline in AHI and SaO 2, but might increase central apneas and cause oxygen desaturation in some individuals and should be used with caution.

Studies on wakefulness-promoting effect of memantine in rats

We hypothesized that memantine, an anti-dementia drug, may be useful for the treatment of excessive daytime sleepiness. The effect of memantine on excessive sleepiness after 6h sleep deprivation was studied in comparison with that of methylphenidate, and the involvement of the dopaminergic system in the wakefulness-promoting effect of memantine was also evaluated. Electrodes for electroencephalogram (EEG) and electromyogram (EMG) were chronically implanted into the cortex and dorsal neck muscle, respectively, of adult male rats. EEG and EMG were recorded with an electroencephalograph for 6h (19:00–01:00). After sleep deprivation (13:00–19:00), compensatory excessive sleepiness (19:00–01:00) was observed in rats. Memantine (10mg/kg, p.o.) and methylphenidate (10–30mg/kg, p.o.) caused a significant increase of sleep latency compared with the control group. Furthermore, a significant increase in total awake time and significant decreases in total non-rapid eye movement (NREM) sleep and REM sleep times were observed by administration of memantine (3–10mg/kg) and methylphenidate (3–30mg/kg) compared with control in sleep deprivation rats. Although the effect of memantine was significantly suppressed by D1 receptor antagonist SCH 23390 (0.1mg/kg, i.p.), D2 receptor antagonist raclopride had no antagonistic effect (1mg/kg, i.p.). From these results, the effect of memantine on sleepiness after sleep deprivation was similar to that of methylphenidate, and D1 receptor may be involved in the effect of memantine.

The nightly administration of sodium oxybate results in significant reduction in the nocturnal sleep disruption of patients with narcolepsy

Background Previous studies indicate that nightly sodium oxybate administration reduces nocturnal sleep disruption in narcolepsy. The present study provided an opportunity to further characterize these sleep-related effects in patients with narcolepsy during treatment with sodium oxybate as monotherapy or in combination with modafinil. Methods This double-blind, placebo-controlled study enrolled 278 patients with narcolepsy taking modafinil 200–600 mg daily for the treatment of excessive daytime sleepiness (EDS). Following a baseline polysomnogram (PSG) and Maintenance of Wakefulness Test (MWT), patients were randomized to receive treatment with: (1) placebo, (2) sodium oxybate, (3) modafinil, or (4) sodium oxybate + modafinil. PSGs and MWTs were repeated after 4 and 8 weeks. Other efficacy measures included Epworth Sleepiness Scale scores and daily diary recordings. Results After 8 weeks, significant changes in sleep architecture among patients receiving sodium oxybate and sodium oxybate/modafinil included a median increase in Stage 3 and 4 sleep (43.5 and 24.25 min, respectively) and delta power and a median decrease in nocturnal awakenings (6.0 and 9.5, respectively). No significant changes in PSG parameters were noted in patients treated with placebo or modafinil alone. Conclusions In addition to its established efficacy for the treatment of cataplexy and EDS, nightly sodium oxybate administration significantly reduces measures of sleep disruption and significantly increases slow-wave sleep in patients with narcolepsy.

Effects of modafinil: studies on cocaine self‐administration, neurochemistry, and activity in rhesus macaques.

Modafinil is currently used as a treatment for excessive daytime sleepiness. Increasing evidence suggests modafinil affects the dopamine transporter. Therefore, we examined the effects of modafinil (10 mg/kg; i.v.) on daytime locomotor activity, cocaine self‐administration, reinstatement of cocaine‐maintained behavior, and extracellular dopamine levels. Locomotor activity was measured in the home cage using Actiwatch telemetry, with four days of baseline recording preceding a morning injection. Administration of modafinil did not significantly increase daytime locomotor activity. Monkeys self‐administered cocaine under a second order, fixed ratio 20 schedule; pretreatment with modafinil did not have a significant effect on cocaine self‐administration. Cocaine maintained responding was then extinguished and extinction level responding maintained for a minimum of two days before priming with modafinil. Modafinil was able to significantly reinstate extinguished cocaine‐maintained behavior. Finally, dopamine levels following modafinil administration were measured using in vivo microdialysis followed by sample analysis using high performance liquid chromatography. Modafinil significantly increased dopamine overflow within the caudate nucleus approximately 20 minutes after injection. PET imaging will determine DAT occupancy associated with behavioral and neurochemical effects. Modafinil did not appear to have behavioral stimulant effects at 10 mg/kg, but at this dose does appear to have dopaminergic effects as measured by in vivo neurochemistry and cocaine reinstatement assays.

Conception, Pregnancy, Delivery, and Breastfeeding in a Narcoleptic Patient with Cataplexy

Conception, Pregnancy, Delivery, and Breastfeeding in a Narcoleptic Patient with Cataplexy

The Differential Diagnosis of Excessive Daytime Sleepiness and Cognitive Deficits in a Patient with Delirium, Schizophrenia and Possible Narcolepsy: A Case Report

Narcolepsy and schizophrenia are disorders which share common features of negative symptoms, excessive daytime sleepiness and cognitive deficits. Presented here is a case report of a fifty-nine year old man with a past medical history of schizophrenia who was evaluated for suspected symptoms of delirium. After an electroencephalogram was performed with surprising results, the patient's differential diagnosis included schizophrenia with comorbid narcolepsy. We present emerging evidence that excessive daytime sleepiness and attentional deficits in both narcolepsy and schizophrenia may share a common pathophysiological pathway through orexin deficiency and its effects on the dopamine system. Finally, we discuss the potential for modafinil as a treatment for excessive daytime sleepiness and attentional problems in schizophrenia and narcolepsy.

Behavioral responses of dopamine β-hydroxylase knockout mice to modafinil suggest a dual noradrenergic–dopaminergic mechanism of action

Modafinil is approved for use in the treatment of excessive daytime sleepiness. The precise mechanism of modafinil action has not been elucidated, although both dopamine (DA) and norepinephrine (NE) systems have been implicated. To explore the roles of DA and NE in the mechanism of modafinil-induced arousal, dopamine β-hydroxylase knockout ( Dbh −/−) mice were examined in behavioral paradigms of arousal (photobeam breaks and behavioral scoring of sleep latency). Dbh −/− mice completely lack NE but have hypersensitive DA signaling. It was hypothesized that Dbh −/− mice would be unresponsive to modafinil if the compound acts primarily via NE, but would be hypersensitive to modafinil if it acts primarily via DA. Dbh −/− mice had increased sensitivity to the locomotor-activating and wake-promoting effects of modafinil. Paradoxically, the α1-adrenergic receptor antagonist, prazosin, attenuated the effects of modafinil in control mice, but not in Dbh −/− mice. Blockade of DA receptors with flupenthixol decreased modafinil-induced locomotion and wake in both control and Dbh −/− mice. These results suggest that both NE and DA are involved in the behavioral effects of modafinil in control mice, but the requirement for NE can be bypassed by hypersensitive DA signaling.

Narcolepsy: current treatment options and future approaches

The management of narcolepsy is presently at a turning point. Three main avenues are considered in this review: 1) Two tendencies characterize the conventional treatment of narcolepsy. Modafinil has replaced methylphenidate and amphetamine as the first-line treatment of excessive daytime sleepiness (EDS) and sleep attacks, based on randomized, double blind, placebo-controlled clinical trials of modafinil, but on no direct comparison of modafinil versus traditional stimulants. For cataplexy, sleep paralysis, and hypnagogic hallucinations, new antidepressants tend to replace tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) in spite of a lack of randomized, double blind, placebo-controlled clinical trials of these compounds; 2) The conventional treatment of narcolepsy is now challenged by sodium oxybate, the sodium salt of gammahydroxybutyrate, based on a series of randomized, double-blind, placebo-controlled clinical trials and a long-term open label study. This treatment has a fairly good efficacy and is active on all symptoms of narcolepsy. Careful titration up to an adequate level is essential both to obtain positive results and avoid adverse effects; 3) A series of new treatments are currently being tested, either in animal models or in humans, They include novel stimulant and anticataplectic drugs, endocrine therapy, and, more attractively, totally new approaches based on the present state of knowledge of the pathophysiology of narcolepsy with cataplexy, hypocretine-based therapies, and immunotherapy.

Aktuelle Therapie der Narkolepsie

Die Behandlung der Narkolepsie hat durch die Verfügbarkeit neuer Medikamente in den letzten Jahren einen Wandel erfahren. Basierend auf der „International Classification of Sleep Disorders” (ICSD-2) der amerikanischen Academy of Sleep Medicine von 2005 werden die klinischen Symptome, Genetik, Pathophysiologie und das aktuelle diagnostische Vorgehen zusammengefasst und die aktuellen Therapiemöglichkeiten basierend auf den europäischen und deutschen Leitlinien dargestellt. Seitdem Natriumoxybat und Modafinil in der Behandlung der Narkolepsie zugelassen sind, haben sich die Empfehlungen für die Therapie verändert und ehemalige Medikamente der 1. Wahl sind nun erst zweitrangig in Betracht zu ziehen. Zur Therapie der Tagesschläfrigkeit als ein Hauptsymptom der Narkolepsie mit und ohne Kataplexien wird nun Modafinil, Methylphenidat und Natriumoxybat empfohlen, Amphetamine und Selegilin sind Medikamente der 2. Wahl. Die Europäische Leitlinie zur Therapie der Narkolepsie empfiehlt nun zur Therapie der Kataplexie Natriumoxybat und erst in zweiter Linie Antidepressiva, einschließlich Clomipramin und Selegilin. Auch zur Therapie des gestörten Nachtschlafes wird Natriumoxybat empfohlen und bietet so die beste Alternative zur Therapie aller Narkolepsiesymptome.

Upregulating substance P levels to treat obstructive sleep apnea

Background: The neuropeptide (tachykinin) substance P is widely distributed in the central and peripheral nervous systems. Substance P has been suggested to function as a neurotransmitter, cotransmitter, or neuromodulator in the central and peripheral nervous system. substance P also influences sleep physiology. Neurokinin 1 (NK-1) receptors may also be implicated in the control of sleep/wake behavior. Obstructive sleep apnea syndrome (OSAS) is defined as repeated episodes of upper airway occlusion during sleep with subsequent excessive daytime sleepiness (EDS). Subsatance P levels are found to be significantly lowered in patients with OSAS. Objective: The aim of this review was to investigate the relationship between substance P, EDS and other OSAS complications. Methods: The literature was searched using standard methods. Medline and Embase were searched systematically from 1974 to the end of February 2008 for relevant articles published in English. Results/conclusion: EDS seen in some OSAS patients may be associated with various pathophysiological mechanisms including changes in substance P levels. Intravenous substance P administration in OSAS patients can be effective in the treatment of EDS. Further studies on the possible relationship between low serum substance P and hypertension, reproductive function disorders, memory and learning problems in OSAS cases is required.

A Predictive Model for Fatigue and Its Etiologic Associations in Primary Biliary Cirrhosis

Excessive day-time somnolence and autonomic dysfunction are biological processes prevalent in Primary Biliary Cirrhosis (PBC) that associate with fatigue. Here we explore how these biological associates inter-relate, and their cumulative impact upon typical clinical cohorts. A predictive model for daytime hypersomnolence (Epworth Sleepiness Scale (ESS)) and autonomic dysfunction (Orthostatic Grading Scale (OGS)) was developed in a derivation cohort (n=124) and subsequently validated in a second cohort (n=114). Subjects also completed the disease specific quality of life tool, the PBC-40. A composite predictive criterion (presence of either ESS > or =10 or OGS > or =4) for the presence of fatigue in PBC patients had a sensitivity of 0.71 (95% confidence intervals 0.59-0.81) and specificity 0.8 (0.67-0.9) (positive predictive value (PV); 0.84 (0.72-0.92), negative PV; 0.66 (0.53-0.78) for moderate or severe fatigue). Ninety-seven percent of severely fatigued patients (0% of non-fatigued) met the aetiology predictive criterion (chi(2) 49.6, P<.0001). Expression of both significant daytime somnolence and autonomic dysfunction was not associated with more severe fatigue, suggesting that there is a threshold effect for fatigue in PBC. When applied to a second independent cohort, the composite criterion retained strongly significant predictive value for fatigue. A significant proportion of fatigue in PBC associates with one or both of autonomic dysfunction (OGS > or =4) and sleep disturbance (ESS > or =10). Those meeting both ESS and OGS criteria were not more severe fatigued than those meeting the diagnostic criterion for either OGS or ESS alone. A threshold effect for fatigue has implications for potential therapeutic interventions.

Sodium oxybate: Efficacy, safety and tolerability in the treatment of narcolepsy with or without cataplexy

Sodium oxybate is the sodium salt of gamma- hydroxybutyrate, an endogenous cerebral inhibitory neurotransmitter. It is licensed in the United States for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy and in the European Union for the treatment of narcolepsy with cataplexy. Its mode of action is uncertain, but it increases 5-hydroxytryptamine turnover, interacts with opioid systems and may act as a gamma-aminobutyric acid B receptor agonist (GABA(B)). It is rapidly absorbed and eliminated, having a mean elimination half-life of 30-60 minutes. In controlled trials in narcolepsy without cataplexy, it decreased excessive daytime sleepiness and increased several quality of life domains. In combination with modafinil, it exerted an additive effect in diminishing daytime sleepiness. Both acute (four to eight weeks) and chronic (12 months) studies have demonstrated sodium oxybate's efficacy in decreasing cataplectic attack frequency. It is well tolerated with adverse event withdrawal rates of approximately 3-10% after acute and chronic administration. There is no clear evidence of a withdrawal syndrome after abrupt cessation of therapeutic doses. Sodium oxybate appears to be an effective and well-tolerated treatment for all the key symptoms of the two forms of narcolepsy.

An inverse agonist of the histamine H 3 receptor improves wakefulness in narcolepsy: Studies in orexin −/− mice and patients

Narcolepsy is characterized by excessive daytime sleepiness (EDS), cataplexy, direct onsets of rapid eye movement (REM) sleep from wakefulness (DREMs) and deficiency of orexins, neuropeptides that promote wakefulness largely via activation of histamine (HA) pathways. The hypothesis that the orexin defect can be circumvented by enhancing HA release was explored in narcoleptic mice and patients using tiprolisant, an inverse H 3-receptor agonist. In narcoleptic orexin −/− mice, tiprolisant enhanced HA and noradrenaline neuronal activity, promoted wakefulness and decreased abnormal DREMs, all effects being amplified by co-administration of modafinil, a currently-prescribed wake-promoting drug. In a pilot single-blind trial on 22 patients receiving a placebo followed by tiprolisant, both for 1 week, the Epworth Sleepiness Scale (ESS) score was reduced from a baseline value of 17.6 by 1.0 with the placebo ( p > 0.05) and 5.9 with tiprolisant ( p < 0.001). Excessive daytime sleep, unaffected under placebo, was nearly suppressed on the last days of tiprolisant dosing. H 3-receptor inverse agonists could constitute a novel effective treatment of EDS, particularly when associated with modafinil.

Modafinil in the treatment of excessive daytime sleepiness.

Modafinil (Provigil) is approved for treating excessive daytime sleepiness associated with narcolepsy, for shift-work sleep disorder, and as an adjunctive treatment in patients with obstructive sleep apnea syndrome who have residual daytime sleepiness despite optimal treatment with continuous positive airway pressure. Although modafinil improves measures of sleepiness, it does not generally normalize them, and it may be less effective than other stimulants for some narcoleptic patients. We need head-to-head comparisons of modafinil with traditional stimulants in humans to better define its role. We review the current approved and off-label uses of this drug and the evidence behind them.

A Randomized, Double-Blind, Placebo-Controlled Trial of Modafinil for Negative Symptoms in Schizophrenia

Negative symptoms are core features of schizophrenia that are functionally debilitating, associated with poor outcomes, and resistant to existing pharmacotherapies. We performed a randomized, double-blind, placebo-controlled study of modafinil, a medication approved for the treatment of excessive daytime sleepiness, to explore its efficacy as an adjunctive therapy for negative symptoms in schizophrenia. Twenty subjects with DSM-IV schizophrenia or schizoaffective disorder were randomly assigned to double-blind treatment with modafinil or placebo for 8 weeks. The study ran from March 2002 through March 2006. Outcome measures included the Scale for the Assessment of Negative Symptoms (SANS), Brief Psychiatric Rating Scale (BPRS), Clinical Global Impressions (CGI) scale, Quality of Life Interview, neurocognitive assessments (California Verbal Learning Test, Degraded Performance-Continuous Performance Test, Trail-Making Test B), and somatic measures (sleep, weight, side effects). Modafinil treatment was associated with a greater rate (CGI-Improvement [CGI-I] score < or = 3, 7/10 vs. 1/10) and degree (mean CGI-I score, 3.2 vs. 4.1) of global improvement at study endpoint compared with placebo. However, modafinil did not significantly improve global negative symptoms as measured by the total SANS or SANS individual global items. Modafinil did not significantly worsen psycho-pathology (according to the BPRS), compared with placebo, and was well tolerated. Although no effect on negative symptoms was found, adjunctive therapy with modafinil may result in global improvements in patients with schizophrenia who have prominent negative symptoms.

EFNS guidelines on management of narcolepsy

Management of narcolepsy with or without cataplexy relies on several classes of drugs, namely stimulants for excessive daytime sleepiness and irresistible episodes of sleep, antidepressants for cataplexy and hypnosedative drugs for disturbed nocturnal sleep. In addition, behavioral measures can be of notable value. Guidelines on the management of narcolepsy have already been published. However contemporary guidelines are necessary given the growing use of modafinil to treat excessive daytime sleepiness in Europe within the last 5-10 years, and the decreasing need for amphetamines and amphetamine-like stimulants; the extensive use of new antidepressants in the treatment of cataplexy, apart from consistent randomized placebo-controlled clinical trials; and the present re-emergence of gamma-hydroxybutyrate under the name sodium oxybate, as a treatment of all major symptoms of narcolepsy. A task force composed of the leading specialists of narcolepsy in Europe has been appointed. This task force conducted an extensive review of pharmacological and behavioral trials available in the literature. All trials were analyzed according to their class evidence. Recommendations concerning the treatment of each single symptom of narcolepsy as well as general recommendations were made. Modafinil is the first-line pharmacological treatment of excessive daytime sleepiness and irresistible episodes of sleep in association with behavioral measures. However, based on several large randomized controlled trials showing the activity of sodium oxybate, not only on cataplexy but also on excessive daytime sleepiness and irresistible episodes of sleep, there is a growing practice in the USA to use it for the later indications. Given the availability of modafinil and methylphenidate, and the forseen registration of sodium oxybate for narcolepsy (including excessive daytime sleepiness, cataplexy, disturbed nocturnal sleep) in Europe, the place of other compounds will become fairly limited. Since its recent registration cataplexy sodium oxybate has now become the first-line treatment of cataplexy. Second-line treatments are antidepressants, either tricyclics or newer antidepressants, the later being increasingly used these past years despite few or no randomized placebo-controlled clinical trials. As for disturbed nocturnal sleep the best option is still hypnotics until sodium oxybate is registered for narcolepsy. The treatments used for narcolepsy, either pharmacological or behavioral, are diverse. However the quality of the published clinical evidences supporting them varies widely and studies comparing the efficacy of different substances are lacking. Several treatments are used on an empirical basis, specially antidepressants for cataplexy, due to the fact that these medications are already used widely in depressed patients, leaving little motivation from the manufacturers to investigate efficacy in relatively rare indications. Others, in particular the more recently developed substances, such as modafinil or sodium oxybate, are evaluated in large randomized placebo-controlled trials. Our objective was to reinforce the use of those drugs evaluated in randomized placebo-controlled trials and to reach a consensus, as much as possible, on the use of other available medications.

Sodium Oxybate Improves Excessive Daytime Sleepiness in Narcolepsy

To assess the effectiveness of sodium oxybate therapy, modafinil therapy and the combination of the two for excessive daytime sleepiness in narcolepsy patients previously taking modafinil. Double-blind, placebo-controlled, multicenter study. Forty-four sites in the United States, Canada, the Czech Republic, France, Germany, the Netherlands, Switzerland, and the United Kingdom. Two hundred seventy- adult patients with narcolepsy taking 200 to 600 mg of modafinil daily for the treatment of excessive daytime sleepiness. Patients received unchanged doses of modafinil (with sodium-oxybate placebo) during a 2-week baseline phase. Following a baseline polysomnogram and Maintenance of Wakefulness Test, they were randomly assigned to 1 of 4 treatment groups: sodium-oxybate placebo plus modafinil placebo, sodium oxybate plus modafinil placebo, modafinil plus sodium-oxybate placebo, or sodium oxybate plus modafinil. Sodium oxybate was administered as 6 g nightly for 4 weeks and was then increased to 9 g nightly for 4 additional weeks. The primary efficacy measure was the Maintenance of Wakefulness Test; secondary measures included the Epworth Sleepiness Scale, diary recordings, and the Clinical Global Impression-change scale. Following the switch from modafinil to placebo, the mean average daytime sleep latency on the Maintenance of Wakefulness Test decreased from 9.74 minutes at baseline to 6.87 minutes after 8 weeks (p < .001). In the sodium-oxybate group, there was no decrease in sleep latency, suggesting that this drug was as efficacious in treating the excessive daytime sleepiness as the previously administered modafinil. In contrast, the sodium-oxybate/modafinil group demonstrated an increase in daytime sleep latency from 10.43 minutes to 13.15 minutes (p < .001), suggesting that this combination of drugs produced an additive effect. The sodium-oxybate group also demonstrated a decrease in median average Epworth Sleepiness Scale scores, from 15 to 12.0, whereas the sodium-oxybate/modafinil group decreased from 15.0 to 11.0 (for both, p < .001). The Clinical Global Impression-Change scale demonstrated similar results. Sodium oxybate and modafinil are both effective for treating excessive daytime sleepiness in narcolepsy, producing additive effects when used together. Sodium oxybate is beneficial as both monotherapy and as adjunctive therapy for the treatment of excessive daytime sleepiness in narcolepsy.

Formulary Forum: Sodium Oxybate for Cataplexy

To review the pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, precautions, dosing recommendations, and patient counseling of sodium oxybate for the treatment of cataplexy in patients with narcolepsy. OVID and PubMed databases were searched (1966-January 2006) using the key words sodium oxybate, gamma-hydroxybutyrate, narcolepsy, and cataplexy. Only English-language articles were selected. All information on sodium oxybate related to narcolepsy and cataplexy was considered. Study selection included human trials evaluating safety and efficacy of sodium oxybate for the treatment of cataplexy. Sodium oxybate is approved by the Food and Drug Administration for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy. In placebo-controlled trials, sodium oxybate demonstrated efficacy in reducing the number of cataplexy attacks. The dosing regimen includes a split dose given at bedtime and 2.5-4 hours later due to its short elimination half-life. The drug is generally well tolerated, with headache, nausea, dizziness, pain, and somnolence being the most common adverse events. Sodium oxybate is safe and effective for the treatment of cataplexy. Potential disadvantages include a multiple dosing regimen, abuse potential, cost, and a closed distribution system. Potential advantages demonstrated in clinical trials include significant decreases in the number of weekly cataplexy attacks, improvement in daytime sleepiness, and improvement in the Clinical Global Impression of Change score and nighttime awakenings. Overall, sodium oxybate provides a new option for the treatment of cataplexy.

A Double-Blind, Placebo-Controlled Study Demonstrates Sodium Oxybate Is Effective for the Treatment of Excessive Daytime Sleepiness in Narcolepsy

A Double-Blind, Placebo-Controlled Study Demonstrates Sodium Oxybate Is Effective for the Treatment of Excessive Daytime Sleepiness in Narcolepsy