Once-Nightly Sodium Oxybate (FT218) Demonstrated Improvement of Symptoms in a Phase 3 Randomized Clinical Trial in Patients With Narcolepsy

Study Objectives To assess the efficacy and safety of FT218, a novel once-nightly formulation of sodium oxybate (ON-SXB), in patients with narcolepsy in the phase 3 REST-ON trial. Methods Narcolepsy patients aged ≥16 years were randomized 1:1 to uptitration of ON-SXB (4.5, 6, 7.5, and 9 g) or placebo. Three coprimary endpoints were change from baseline in mean sleep latency on the Maintenance of Wakefulness test, Clinical Global Impression-Improvement rating, and weekly cataplexy attacks at 9, 7.5, and 6 g. Secondary endpoints included change from baseline on the Epworth Sleepiness Scale. Safety included adverse drug reactions and clinical laboratory assessments. Results In total, 222 patients were randomized; 212 received ≥1 dose of ON-SXB (n=107) or placebo (n=105). For the 3 coprimary endpoints and Epworth Sleepiness Scale, all 3 doses of ON-SXB demonstrated clinically meaningful, statistically significant improvement vs placebo (all P<0.001). For ON-SXB 9 g vs placebo, increase in mean sleep latency was 10.8 vs 4.7 min (LSMD [95% CI], 6.13 [3.52–8.75]), 72.0% vs 31.6% were rated much/very much improved on Clinical Global Impression-Improvement (OR [95% CI], 5.56 [2.76–11.23]), change in mean weekly number of cataplexy attacks was –11.5 vs –4.9 (LSMD [95% CI], –6.65 [–9.32 to –3.98]), and change in Epworth Sleepiness Scale was –6.5 and –2.7 (LSMD [95% CI], –6.52 [–5.47 to –2.26]). Common adverse reactions included nausea, vomiting, headache, dizziness, and enuresis. Conclusions ON-SXB significantly improved narcolepsy symptoms; its safety profile was consistent with SXB. ON-SXB conferred efficacy with a clearly beneficial single nighttime dose.

489 Pivotal Phase 3 Study of FT218, a Once-Nightly Sodium Oxybate Formulation, in Patients With Narcolepsy: REST-ON Primary Results

Introduction Sodium oxybate (SO) is an effective treatment for patients with narcolepsy; however, currently available SO formulations require twice-nightly dosing. The purpose of this study was to evaluate efficacy and safety of FT218, an investigational once-nightly controlled-release SO formulation, for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy types 1 (NT1) and 2 (NT2). Methods This was a randomized, double-blind, placebo-controlled, multicenter study in patients with narcolepsy ≥16 years old. Patients were randomized 1:1 to receive FT218 or matching placebo: 4.5 g/night for 1 week, 6.0 g/night for 2 weeks, 7.5 g/night for 5 weeks, and 9.0 g/night for 5 weeks (maximum treatment duration, 13 weeks). Coprimary endpoints were mean sleep latency (minutes) on maintenance of wakefulness test (MWT), Clinical Global Impression-Improvement (CGI-I) of sleepiness, and weekly number of cataplexy attacks (NCAs; NT1 only). Results A total of 212 patients were randomized and received study treatment (FT218, n=107; placebo, n=105). FT218 showed significant (P<0.001) improvement vs placebo in mean sleep latency on MWT for all evaluated doses; LS mean difference (minutes) between FT218 and placebo was 6.13 at 9.0 g (week 13), 6.21 at 7.5 g (week 8), and 4.98 at 6.0 g (week 3). A higher proportion of patients receiving FT218 were much/very much improved on CGI-I vs placebo (72% vs 31.6% at 9.0 g; 62.6% vs 22.8% at 7.5 g; and 40.1% vs 6.1% at 6.0 g; all P<0.001). LS mean difference between FT218 and placebo in mean weekly NCAs was significant (P<0.001) for all doses: −6.65 at 9.0 g, −6.27 at 7.5 g, and −4.83 at 6.0 g. The most common adverse reactions were nausea, vomiting, headache, dizziness, enuresis, and decreased appetite. Conclusion All evaluated doses of FT218 showed significant improvement vs placebo in mean sleep latency on MWT, CGI-I, and weekly NCAs. FT218 was generally well tolerated and the most common adverse events were consistent with known side effects of SO. Support (if any) Avadel Pharmaceuticals.

A comparative study to assess the satisfaction with clinical outcome of the patients suffering from hemiplegic shoulder subluxation and undergoing rehabilitation with and without Bobath shoulder sling

Background: Hemiplegic shoulder subluxation is one of the most common factor for post-stroke upper limb disability. There are various ways to assess its outcome during rehabilitation, but the assessment of patients’ satisfaction with the shoulder support is often missed. This study was done to compare those patients’ satisfaction with clinical outcome who were undergoing same rehabilitation programme for their hemiplegic shoulder subluxation with and without Bobath shoulder sling.Methods: This prospective controlled interventional study was conducted on 30 patients of both sexes within the age group of 45-65 years with hemiplegic (duration <6 weeks) gleno-humeral subluxation (GHS). Screening of GHS was done by palpation. They were randomly divided in two groups of same number (15 in each group) and put on rehabilitation protocol with group 1 receiving Bobath shoulder Sling as support for subluxed shoulder and group 2 continuing without it. Patients’ satisfaction on clinical outcome was measured with clinical global impression-improvement (CGI-I) scale. Data were collected at 6 weeks (first follow up-visit), 12 weeks (visit 2) and at the end of the study i.e. 24 weeks (visit 3).Results: Statistically significant difference (p=0.003) in mean score of CGI-I at visit 1 suggested significant improvement for group 1 but no statistically significant difference in improvement was noticed between the groups at visit 2 (p=1.000) and visit 3 (p=0.724).Conclusions: Use of support for hemiplegic shoulder is beneficial only during early days of rehabilitation, not on prolonged use.

Assessing the severity of psychiatric disorders using the Health of the Nation Outcome Scales: An equipercentile linking analysis

Objective: The Health of the Nation Outcome Scales was developed as an overall measure of mental health, applicable to the complete range of psychiatric disorders. Meanwhile, it is a benchmark tool for service providers and is also used for the allocation of costs and funding. The ability of the Health of the Nation Outcome Scales to assess and differentiate the severity of psychiatric disorders is largely unknown, as it is the interpretation of a change in score. We aim to establish Health of the Nation Outcome Scales cut-off and benchmark values for severity and improvement – respectively change, using equipercentile linking to the Clinical Global Impression scales. Methods: In a clinical sample of 30,616 individuals with a psychiatric disorder, we used a multivariate regression analysis to determine the correlation between the scales and possible confounders. We used an equipercentile linking analysis of the Clinical Global Impressions severity scale with the Health of the Nation Outcome Scales sum score to establish cut-off values for severity. The linking of the Health of the Nation Outcome Scales sum score difference and the percentage of change to the Clinical Global Impression improvement scale determined benchmark values for change (i.e. improvement or deterioration). Results: The Health of the Nation Outcome Scales and Clinical Global Impression scales showed a Spearman correlation of 0.38 ( p < 0.000). Clinical Global Impression–Severity: ‘borderline-ill’ corresponded to Health of the Nation Outcome Scales score 3–5; ‘mildly ill’ to 6–10; ‘moderately ill’ to 11–16; ‘markedly ill’ to 17–25; ‘severely ill’ to 26–35; and ‘extremely ill’ to a score ⩾36. The Spearman correlation between the percentage change of the Health of the Nation Outcome Scales was 0.39 ( p > 0.000); Clinical Global Impression–Improvement: ‘minimally improved’ corresponded to Health of the Nation Outcome Scales reduction of 4 points or 9%; ‘much-improved’ to 12 points or 48%; ‘very-much-improved’ to ⩾20 points or ⩾90%. Clinical Global Impression–Improvement: ‘minimally worse’ corresponded to an increase of 6 points or 25%; ‘much-worse’ to 12 points or 54%; and finally, ‘very-much-worse’ to >18 points or ⩾82%. Conclusion: Our results allow for the comparison of severity and response to treatment of patients with a psychiatric disorder, independent of diagnosis.

Augmentation of clozapine with ECT: a retrospective case analysis

Objective: We sought to assess the effectiveness of clozapine augmentation with Electroconvulsive therapy (ECT) (C+ECT) in patients with clozapine-resistant schizophrenia. Methods: We conducted a retrospective review of electronic health records to identify patients treated with C+ECT. We determined the response to C+ECT and the rate of rehospitalisation over the year following treatment with C+ECT. Results: Forty-two patients were treated with C+ECT over a 10-year period. The mean age of the patients at initiation of ECT was 46.3 (SD = 8.2) years (range 27–62 years). The mean number of ECTs given was 10.6 (SD = 5.3) (range 3–25) with the majority receiving twice weekly ECT. Seventy-six per cent of patients (n = 32) showed a Clinical Global Impression-Improvement (CGI-I) score of ≤3 (at least minimally improved) following C+ECT. The mean number of ECT treatments was 10.6 (SD = 5.3) (range 3–25) with the majority receiving twice weekly ECT. Sixty-four per cent of patients experienced no adverse events. Response to C+ECT was not associated with gender, age, duration of illness or duration of clozapine treatment. Seventy-five per cent of responders remained out of hospital over the course of 1-year follow-up, while 70% of those with no response to C+ECT were not admitted to hospital. Three patients received maintenance ECT, one of whom was rehospitalised. Conclusion: This study lends support to emerging evidence for the effectiveness of C+ECT in clozapine-resistant schizophrenia. These results are consistent with the results of a meta-analysis and the only randomised controlled trial (RCT) of this intervention. Further RCTs are required before this treatment can be confidently recommended.

Aripiprazole in youth with intellectual disabilities: A retrospective chart study

A retrospective chart study of patients on open-label aripiprazole treatment was conducted in the Netherlands to add to the knowledge of aripiprazole in children and young adults with mild and borderline intellectual disabilities (IDs). Fifty-three youths, mean age 14.7 ± 3.4 years and mean IQ 64.5 ±13.8, were included. Treatment responders were defined as “much improved” or “very much improved” based on the Clinical Global Impression -Improvement scale. For 83% of the patients, disruptive behavior was the main target symptom. The overall response rate was 30% after 1–4 weeks and 69% after 5–8 weeks. The 5–8 weeks responders showed a response rate of 64% at 22–26 weeks. Mild adverse events were observed in 53% of the patients of which fatigue and weight gain were the most common. Seven patients (13.2%) discontinued because of adverse events. In 53 children and young adults with mild and borderline IDs, aripiprazole was effective in both the short and the long term. No serious adverse events were observed.

Effectiveness analysis of antipsychotics in schizophrenia using psychometric scales: an observational study

Background: Schizophrenia is a commonest and one of the well known psychiatric disorders. Life expectancy of a patient with schizophrenia may be 20 to 30 years shorter than the general population. Long term antipsychotic therapy is usually required for the management of schizophrenia. It is not currently possible to predict which antipsychotic may be optimal for a given patient because there are still many debates about effectiveness and efficacy of atypical drugs over first generation antipsychotics. So, our aim is to assess the effectiveness of various antipsychotics by using various psychometric scales, which will be helpful to bring out better treatment options for schizophrenia patients.Methods: This was an observational questionnaire based study, conducted on patients of inpatient and outpatient Department of Psychiatry and Department of Pharmacology at VIMSAR, Burla, for a period of 24 months (September 2015 to August 2017). Patients of schizophrenia aged 18 years or above were subjected to clinical global impression – severity scale (CGI-S) and clinical global impression – improvement scale (CGI-I) questionnaire after taking informed consent. Then scores were calculated using non parametric test with Graph pad Prism version 6.0.Results: Out of the 90 cases, majority (60) of patients belonged to the middle (25 to 45 yrs) age group followed by 20 younger (<25 yrs) age group and rest 10 were elderly (>45 yrs) patients. Both scales showed significant improvement with atypical antipsychotics as compared to first generation antipsychotics.Conclusions: Based on these findings, we can conclude that atypical antipsychotics are more effective than first generation antipsychotics. But further studies are needed to assist clinicians in making optimum treatment decisions.

Analysis of Factors Influencing the Efficiency of Acupuncture in Tinnitus Patients

An effective acupuncture treatment must comprehend the influence of various factors, but studies in this aspect remain limited. This study aimed to identify relevant factors and search for the best practical method of acupuncture for patients with tinnitus. The study was a retrospective review of patients’ data with a prospective design who had subjective idiopathic tinnitus and received acupuncture between May 2012 and August 2017. Patients’ demographics, tinnitus characteristics, previous diseases, underlying diseases, oral habits, audiograms, acupuncture sessions, and acupoints were recorded and analyzed. A visual analog scale (VASloudness) was used for measuring the loudness of tinnitus, and the Clinical Global Impression-Improvement scale (CGI-I) was used for assessing the suffering of patients. Good treatment responses in patients were defined as the magnitude of change from the baseline VASloudness for ≥ 30% plus CGI-I ≤ 3 points. In total, 107 patients were enrolled. Most factors were not significantly associated with the treatment effectiveness of acupuncture in tinnitus patients. Only the combination of acupoints and the number of acupuncture sessions reached statistically significant differences. Further analyzing these two factors, we confirmed that the combination of periauricular and distal acupuncture and 17 to 24 acupuncture sessions contributed to a considerably better outcome. This result would serve as a reference for clinical acupuncturists to select an appropriate acupuncture strategy in the treatment of tinnitus.

Disruptive behaviour's treatment with paliperidone in autistic disorder: Review and case report

IntroductionAutistic disorder (AD) is a neuropsychiatric disorder that often presents significant disruptive symptoms such as irritability, aggression and self-injury in addition to impairment of social skills and communication. These symptoms interfere both individuals with AD and their families and social environment.ObjectiveShow paliperidone effect in behavioural symptoms in AD.MethodsLiterature review about behavioural symptoms in AD and paliperidone effect in its treatment, followed by a case report of clinical improvement after treatment with paliperidone in a patient with autism. Agitation subscale Aberrant Behavior Checklist (ABC-I) scores was compared prior and 4 weeks after paliperidone treatment, and clinical improvement was assessed with Clinical Global Impression-Improvement Scale (CGI-I).ResultsAlthough risperidone has been one of the most studied atypical antipsychotic to treat this symptoms, its use should be limited in order to avoid extrapyramidal and metabolic symptoms. Paliperidone – the major metabolite of risperidone – has shown effectiveness in the treatment of behavioral symptoms in patients with autism, even in subjects with a prior ineffective trial of risperidone. Our patient, 21-years-old male with AD and significant disruptive symptoms was treated with paliperidone 9 mg/day. We observed a 20-points reduction in ABC-I scores 4 weeks later, with most significant improvement in items like auto-agression, heteroaggressivity, irritability and slams. CGI-I scores showed a much better improvement, and no significant adverse effects appeared.ConclusionsPaliperidone is an effective and safe treatment in behavioral symptoms associated to AD, with reduction in ABC-I subscale scores. More studies are needed to confirm our data.Disclosure of interestThe authors have not supplied their declaration of competing interest.