Correlation of Changes in Patient-Reported Quality of Life With Physician-Rated Global Impression of Change in Patients With Narcolepsy Participating in a Clinical Trial of Sodium Oxybate: A Post Hoc Analysis.

INTRODUCTION: Narcolepsy patients report lower health-related quality of life (HRQoL) than the general population, as measured by the Short Form-36 Health Survey (SF-36). This analysis evaluated whether changes in SF-36 correlated with physician-rated Clinical Global Impression of Change (CGI-C). METHODS: Data were from 209 of 228 narcolepsy patients participating in an 8-week clinical trial of sodium oxybate. Changes from baseline for SF-36 subscales (Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health) and the summary scores were evaluated for correlation with CGI-C overall and by treatment group. Correlations were calculated using the Pearson product-moment correlation coefficient (r). RESULTS: Correlations described an inverse relationship in scores, but a direct relationship in improvement; lower CGI-C scores (i.e., better) were associated with higher SF-36 subscale scores (i.e., improved HRQoL). Moderate and significant correlations were observed for Vitality (r = -0.464; P < 0.0001) and Role Physical (r = -0.310; P < 0.0001) subscales, but weak correlations were observed with other subscales including summary scores. Correlations were stronger at higher sodium oxybate doses for most SF-36 subscales. CONCLUSION: Some aspects of HRQoL, measured by the SF-36, may be associated with narcolepsy. In particular, Vitality (indicative of energy and tiredness) and Role Physical (impact of physical function on daily roles) moderately correlated with overall change in status observed by clinicians. However, lack of strong correlations between SF-36 and CGI-C indicates differences in patient and clinician perspectives of disease, and suggest a need for broader assessment of the impact of narcolepsy and its treatment on patients. FUNDING: Jazz Pharmaceuticals.

Evaluation of Quality of Life in Patients With Narcolepsy Treated With Sodium Oxybate: Use of the 36-Item Short-Form Health Survey in a Clinical Trial.

INTRODUCTION: The present post hoc analysis was designed to evaluate health-related quality of life (HRQoL) using the 36-item Short Form Health Status Survey (SF-36) during an 8-week trial of sodium oxybate (SXB). METHODS: SF-36 was assessed in a phase 3 placebo-controlled trial in patients with narcolepsy (N = 228) randomized to placebo or SXB in doses of 4.5, 6, or 9 g nightly for 8 weeks. Changes from baseline in SF-36 (last observation carried forward) were compared between SXB and placebo, and effect sizes (ES) were estimated. RESULTS: Baseline SF-36 values were lower than normative values for the US general population. After 8 weeks of treatment, mean (±standard deviation) improvement from baseline on the Physical Component Summary (PCS) was significantly greater with SXB 9 g/night than placebo (6.3 ± 9.1 vs. 1.5 ± 6.2; p = 0.005), with moderate ES; no significant difference was found between the SXB and placebo groups on the Mental Component Summary. SXB 9 g/night resulted in significantly (p < 0.05) greater improvements than placebo in Physical Functioning (4.4 ± 9.2 vs. 1.0 ± 8.0), General Health (GH; 3.1 ± 7.0 vs. 0.4 ± 6.8), and Social Functioning (6.8 ± 16.8 vs. 1.1 ± 9.6). All SXB doses resulted in significant improvement (p < 0.05) relative to placebo for Vitality, with moderate ES. No significant differences versus placebo were observed for Role-Physical, Role-Emotional, or Mental Health domains. CONCLUSION: Treatment with SXB was associated with a dose-dependent improvement in HRQoL, with the 9-g nightly dose demonstrating a positive impact on PCS and individual SF-36 domains of Vitality, GH, and Physical and Social Functioning. TRIAL REGISTRATION: NCT00049803. FUNDING: Jazz Pharmaceuticals.

Complex sleep apnea unmasked by the use of a mandibular advancement device.

According to most accepted definitions, complex sleep apnea syndrome (CompSAS) is described as an emergence of central apneas in a patient with obstructive sleep apnea (OSA) upon introduction of continuous positive airway pressure therapy (CPAP). We present two patients who developed comparable central apnea activity when treated with either a CPAP device or a mandibular advancement device. As similar findings have been previously documented in patients with OSA treated with maxillofacial surgery or tracheostomy, we propose that the current definition of CompSAS should broaden to include diagnosis of CompSAS in non-PAP-treated patients, who are managed with either a dental appliance or a surgical procedure.

Exacerbation of cataplexy following gradual withdrawal of antidepressants: manifestation of probable protracted rebound cataplexy.

BACKGROUND: A double-blind, placebo-controlled sodium oxybate trial provided a unique opportunity to compare changes in cataplexy following gradual withdrawal from antidepressants in narcolepsy patients. METHODS: Of 228 enrolled patients, 71 discontinued antidepressant therapy. Data from 57 patients were available for analysis: 37 patients discontinued tricyclic antidepressants (TCAs) and 20 discontinued selective serotonin reuptake inhibitors (SSRIs). The trial included a 21-day withdrawal phase followed by 18-day washout and 14-day single-blind treatment phases. Two additional weeks were permitted for withdrawal from fluoxetine due to its long half-life. Weekly cataplexy attacks were recorded throughout the trial. No historical data on the frequency of cataplexy prior to treatment with antidepressants was available. RESULTS: Among the patients who were and were not withdrawn from antidepressants treatment, the median frequency of baseline weekly cataplexy was similar (17.5 vs. 14.0, respectively). As expected, significant between-group differences emerged by the end of the washout period (52.04 vs. 15.25, respectively; p<0.05); however, the frequency of cataplexy events became similar again by the end of the trial (16.5 vs. 17.5, respectively). CONCLUSIONS: Patients gradually withdrawn from antidepressants experienced a significant increase in cataplexy, but eventually returned to their baseline frequency, comparable to previously untreated control patients. Compared to SSRIs, discontinuation from TCAs was associated with a greater increase in cataplexy attacks.

Weight loss in narcolepsy patients treated with sodium oxybate.

INTRODUCTION: Narcolepsy is often associated with increased body weight. Sodium oxybate has efficacy in many narcolepsy symptoms. The purpose of this study was to evaluate the effects of sodium oxybate on weight in patients with narcolepsy. METHODS: Charts from three centers of all patients with narcolepsy who had been using sodium oxybate for at least 3 months were reviewed. Patients in whom anti-cataplexy medications were added or withdrawn or wake-promoting medications added after the start of sodium oxybate were excluded from further analysis. In the remainder, pre-sodium oxybate and, most recently, on-sodium oxybate weights were compared using Student's t-tests. Sodium oxybate dose and duration of therapy were also noted. RESULTS: A total of 54 patients meeting inclusion criteria were identified. Of these 54, 33 (61%) were women; the mean age was 48.3 years. The mean dose of sodium oxybate was 6.9g/night and the duration of therapy was 25 months. The mean pre-sodium oxybate weight was 78.3 (+/-15.7)kg. The most recent on-sodium oxybate weight was 74.9 (+/-15.1, p=0.003). The average weight loss was 3.4kg, whereas the maximum was 30.9kg. CONCLUSIONS: This study suggests that treatment of patients with narcolepsy with sodium oxybate can result in weight loss.

[Narcolepsy and other hypersomnias].

This article gives an overview of a few most significant but also most frequent primary hypersomnias in humans. The prevalence of hypersomnia in USA is between 0.3 and 16.3% which is close to its prevalence in Europe which is 5-16%. The prevalence of narcolepsy with cataplexy in USA and the countries of Western Europe is from 0.05-0.067%. Its presence is significantly higher in Japan and lower in Israel. Most of the symptoms of narcolepsy represent the abnormal manifestations of dissociated REM sleep process. Excessive daytime sleepiness, sleep attacks and cataplexy are the most frequent symptoms. The diagnosis of narcolepsy should be confirmed by a whole-night polysomnographic recording followed by a Multiple sleep latency test. Idiopathic hypersomnia is a rare disease (ten times as rare as narcolepsy) with the diagnostic procedure similar to that of narcolepsy. Treatment of hypersomnias is symptomatic with the aimed to reduce the most frequent symptoms (excessive daytime sleepiness, sleep attacks, cataplexy and hypnagogic/hypnapompic sleep paralyses).

A pilot study on the effects of sodium oxybate on sleep architecture and daytime alertness in narcolepsy.

STUDY OBJECTIVES: To measure the effect of nocturnal sodium oxybate administration on sleep architecture in patients with narcolepsy. DESIGN: Open-label study. SETTING: Four accredited sleep clinics. PARTICIPANTS: 25 adult patients with narcolepsy-cataplexy. INTERVENTIONS: Patients were weaned from previously used anticataplectic medications and administered increasing nightly doses of sodium oxybate over a 10-week period: 4.5 g for 4 weeks, 6 g for 2 weeks, 7.5 g for 2 weeks, and 9 g for 2 weeks. The effect of sodium oxybate was measured using nocturnal polysomnograms, the Epworth Sleepiness Scale, the Maintenance of Wakefulness Test, and a narcolepsy symptoms questionnaire. RESULTS: The nightly administration of sodium oxybate produced dose-related increases in slow-wave sleep and delta power, rapid eye movement sleep increased initially and then decreased in a dose-related manner, nocturnal awakenings decreased, and daytime sleep latency increased. Significant improvements in daytime symptoms were measured by the Maintenance of Wakefulness Test, the Epworth Sleepiness Scale, and the narcolepsy symptom questionnaire. CONCLUSIONS: Nocturnal administration of sodium oxybate in patients with narcolepsy produces significant improvements in sleep architecture, which coincide with significant improvements in daytime functioning.

Initiating treatment with modafinil for control of excessive daytime sleepiness in patients switching from methylphenidate: an open-label safety study assessing three strategies.

RATIONALE: Modafinil is a first-line wake-promoting medication and a useful therapeutic alternative to psychostimulant medications for excessive daytime sleepiness. OBJECTIVE: This 5-week, randomized, open-label study evaluated three strategies for switching patients from methylphenidate, a commonly used psychostimulant, to modafinil. METHODS: Patients ( n=40) with excessive daytime sleepiness related to narcolepsy, who had received previous treatment with methylphenidate, were switched from methylphenidate to modafinil (200 mg/day followed by 400 mg/day) without a washout period between treatments, with a 2-day washout period between treatments, or by using a taper-down/titrate-up protocol. Adverse events were recorded throughout the study, and Epworth Sleepiness Scale scores were determined at the end of the study. RESULTS: The majority of patients (95%) were successfully switched to modafinil. At the study end point, mean Epworth Sleepiness Scale scores were <12 for each treatment group. All three switching strategies were well tolerated, with adverse events mild or moderate in nature. Adverse events most frequently reported during modafinil treatment were among those seen previously in large-scale, placebo-controlled studies. There were no meaningful differences among the treatment groups in the frequency or severity of adverse events or in their relationship to modafinil treatment. Only one patient discontinued modafinil treatment because of a treatment-related adverse event (i.e. moderate headache); another patient discontinued due to insufficient efficacy. CONCLUSIONS: Switching from methylphenidate to modafinil was well tolerated with or without a washout period or when the methylphenidate dose is gradually tapered during initiation of modafinil therapy. Daytime wakefulness was maintained in patients who have switched from methylphenidate to modafinil. These data suggest that patients with narcolepsy may be switched from methylphenidate to modafinil with few complications and inconveniences.