Efficacy of Oxcarbazepine for Sleep-Related Leg Cramps: A Retrospective Study

Objectives: Sleep-related leg cramps (SRLC) are common among older people. Severe clinical symptoms of SRLC usually cause great discomfort to patients. To date, many treatment drugs have been tried; however, there are currently no drugs approved for treating this condition. We aimed to assess the efficacy of a new drug, oxcarbazepine (OXC), in the treatment of SRLC.Methods: We retrospectively analyzed clinical outcomes following OXC administration. A daily dose of 150 mg OXC was prescribed to control nocturnal leg cramps. Clinical outcomes were measured using the Clinical Global Impression Scale to confirm the effectiveness of OXC.Results: A total of 88.9% (16/18) of patients clinically improved four weeks after OXC prescription, and 94% (15/16) of patients continued to improve at the last follow-up (3–6 months). None of the patients complained of side effects related to 150 mg OXC.Conclusions: OXC may be a new medical option for treatment of SRLC.

Systemic Review on Parkinson’s Disease Medications, Emphasizing on Three Recently Approved Drugs to Control Parkinson’s Symptoms

Parkinson’s Disease (PD) is a disease that involves neurodegeneration and is characterised by the motor symptoms which include muscle rigidity, tremor, and bradykinesia. Other non-motor symptoms include pain, depression, anxiety, and psychosis. This disease affects up to ten million people worldwide. The pathophysiology behind PD is due to the neurodegeneration of the nigrostriatal pathway. There are many conventional drugs used in the treatment of PD. However, there are limitations associated with conventional drugs. For instance, levodopa is associated with the on-off phenomenon, and it may induce wearing off as time progresses. Therefore, this review aimed to analyze the newly approved drugs by the United States-Food and Drug Administration (US-FDA) from 2016–2019 as the adjuvant therapy for the treatment of PD symptoms in terms of efficacy and safety. The new drugs include safinamide, istradefylline and pimavanserin. From this review, safinamide is considered to be more efficacious and safer as the adjunct therapy to levodopa as compared to istradefylline in controlling the motor symptoms. In Study 016, both safinamide 50 mg (p = 0.0138) and 100 mg (p = 0.0006) have improved the Unified Parkinson’s Disease Rating Scale (UPDRS) part III score as compared to placebo. Improvement in Clinical Global Impression—Change (CGI-C), Clinical Global Impression—Severity of Illness (CGI-S) and off time were also seen in both groups of patients following the morning levodopa dose. Pimavanserin also showed favorable effects in ameliorating the symptoms of Parkinson’s Disease Psychosis (PDP). A combination of conventional therapy and non-pharmacological treatment is warranted to enhance the well-being of PD patients.

A Randomized, Double-blind, Placebo-controlled Trial of DL-3-n-butylphthalide in Amyotrophic Lateral Sclerosis Patients

Background: To determine the efficacy and safety of DL-3-n-butylphthalide (NBP) for the treatment of amyotrophic lateral sclerosis (ALS).Methods: A randomized, double-blind, placebo-controlled trial was performed at 19 ALS clinical centers of the Chinese ALS Association. Patients with definite or probable ALS were randomly treated with NBP or placebo for 12 months. The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score was the primary endpoint and was evaluated every 3 months. Secondary endpoints included survival and tracheotomy incidence, total Medical Research Council (MRC) score, percentage of predicted forced vital capacity (FVC), and clinical global impression scale score assessed using the visual analog scale. Results: Between November 23, 2015 and November 22, 2017, 312 ALS patients were enrolled and randomly allocated to either the NBP group (156 patients) or placebo group (156 patients). Ninety-three patients in the NBP group and 92 patients in the placebo group were included in the primary end point analysis. There was no significant difference in the ALSFRS-R score, total MRC score, or clinical global impression between the two groups after treatment. The NBP group exhibited a mild trend of less decrease in the percentage of predicted FVC between baseline and the 12-month visit than the placebo group (least-squares mean change from baseline ± standard error: -7.34±4.28, 95％CI(-15.24,0.56), p=0.0335). Adverse events were reported in 56.5% of patients in the placebo group and 68.8% of patients in the NBP group (χ2=2.99, P=0.0838). No serious adverse event related to treatment occurred.Conclusion: we found no evidence that NBP improved the ALSFRS-R score in patients with ALS. The results suggest a mild trend in the percentage of predicted FVC decreased slowly in the NBP treatment group than in the placebo group.Trial registration: A Multi-center, Randomized, Double Blinding, Placebo-Controlled Clinical Trial of Dl-3-Butylphthalide in the Treatment of Amyotrophic Lateral Sclerosis, ChiCTR-IPR-15007365, Registered 1 November 2015, http://www.chictr.org.cn/showproj.aspx?proj=12354

Case Report: Cariprazine Efficacy in Young Patients Diagnosed With Schizophrenia With Predominantly Negative Symptoms

Negative symptoms of schizophrenia are among the most invalidating clinical manifestations of this disorder, and they are correlated with poorer prognosis, lower quality of life, and fewer chances for successful social reintegration and professional rehabilitation. Although atypical antipsychotics have been associated with higher efficacy on negative symptoms than typical agents, not all of them are equally effective. Cariprazine is a new D3 and D2 receptor partial agonist, and its high D3 affinity may be useful for decreasing several adverse events (e.g., extrapyramidal symptoms or hyperprolactinemia), and also for increasing this drug's efficacy over negative symptoms. This case series presents three young adults with predominantly negative symptoms during treatment with an atypical antipsychotic, administered in stable dose within the therapeutic range, and for at least 4 weeks prior to the cariprazine switch. These patients (two male and one female, mean age 35.7 years) were diagnosed with schizophrenia, according to the DSM-5 criteria. They were evaluated using Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Severity (CGI-S), and Global Assessment of Functioning (GAF). Their mean initial values were 80.3 on PANSS, 4.3 on CGI-S, and 48 on GAF. All these patients were already on a treatment with stable doses of atypical antipsychotics (olanzapine 10 mg/day, n = 1, risperidone 6 mg/day, n = 1, and quetiapine 600 mg/day, n = 1). Cross-titration to cariprazine was initiated, from 1.5 mg qd up to 6 mg qd, during a mean period of 2.7 weeks. After 12 weeks of cariprazine 6 mg/day, the positive scale of PANSS was relatively stable compared to baseline, while the negative mean score decreased by 22%. Also, the mean CGI-S improvement was 15.4% and the GAF mean score increased by 17%. The overall tolerability was good, without severe adverse events being reported. Conclusions: Cariprazine is well tolerated and efficient for patients diagnosed with schizophrenia who have significant negative symptoms that impair daily functioning. After 12 weeks cariprazine succeeded in improving negative symptoms, global functioning, and clinical global impression.

Problematic Substance Use in Adolescent Psychiatric Inpatients: Rates, Clinical Correlates and Effects on Therapeutic Outcomes

Aims: : We aimed to document the clinical rates and correlates of problematic substance use among adolescent inpatients. Background: Adolescents referred to psychiatric inpatient care are likely to present family and social risk factors making them at high-risk of substance use disorder Objective: To document the rates, clinical correlates and effects on therapeutic outcomes of associated problematic substance use in adolescents referred to psychiatric inpatient care. Method: The DEP-ADO questionnaire was used to systematically screen out problematic substance use in two 12-18 adolescent inpatient units between January 2017 and December 2018. Inpatients screened positively based on the DEP-ADO questionnaire and/or information gathered from repeated interviews with the youth and his/her family were reported to the liaison addiction unit for diagnosis. Chart-review procedure was used to document clinical correlates (i.e., suicidal behavior, DSM-5 psychiatric diagnoses, the Clinical Global Impression-Severity score) and therapeutic outcomes (i.e., the Clinical Global Impression-Improvement score, change in Children-Global Assessment Scale score during patients’ stay and length of stay). Result: Over two years, 150 adolescents completed the DEP-ADO questionnaire (Mean Age =14.7 ± 1.7; 42% girls). Thirty percent of adolescent inpatients reported some type of problematic substance use, with a higher likelihood of daily tobacco use (OR=2.4), regular cannabis use (OR=2.3) and occasional opioid/heroin use (OR=9.8) compared to general population. Adolescent inpatients who misused illegal substance prior admission were 2.5 times more likely to report suicidal behaviors. A strong association was reported between binge drinking behavior and a discharge diagnosis of bipolar disorder (OR=11.0). Therapeutic outcomes were not statistically different with regards to alcohol or illicit substance use status. Conclusion: Inpatient adolescents were at high-risk of having associated problematic substance use. Patients with co-existing problematics seem to have more severe and chronic forms of mood disturbances, although the response rate to therapeutics provided during their stay were not lower compared to their counterparts without problematic substance use.

Alcohol-Induced Psychotic Disorder and Depressive Disorder: a Dual Diagnosis Case Series

Alcohol-induced psychotic disorder (AIPD) is a diagnosis in the ICD 10. Previous studies of AIPD do not appear to have reported the co-morbid presence of depressive disorder in either prevalence studies or treatment studies. Five cases are presented with a dual diagnosis of AIPD and depressive disorder. These cases were assessed using the Brief Psychiatric Rating Scale (BPRS), Hamilton Depression Rating Scale (HDRS), Clinical Global Impression Severity score (CGI-S), Clinical Global Impression Improvement score (CGI-I), Drug Attitude Inventory 10 (DAI 10), Short Assessment Personality-Abbreviated Scale (SAPAS) and Modified Sainsbury Tool. Antidepressants and antipsychotics were chosen based on drug attitude scores from DAI 10. Cases demonstrate inpatient and outpatient treatment with good treatment outcomes after six months. Three cases demonstrate suicide risk. The majority did not have a personality disorder. These cases highlight the importance of treating a depressive disorder in AIPD and of tailored medication treatments for poor medication compliance.

A Phase II Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety, and Tolerability of Arbaclofen Administered for the Treatment of Social Function in Children and Adolescents With Autism Spectrum Disorders: Study Protocol for AIMS-2-TRIALS-CT1

Background: Autism Spectrum Disorder (ASD or autism) is characterized by difficulties in social communication and interaction, which negatively impact on individuals and their families' quality of life. Currently no pharmacological interventions have been shown to be effective for improving social communication in autism. Previous trials have indicated the potential of arbaclofen for improving social function among autistic children and adolescents with fluent speech. The AIMS2TRIALS-Clinical Trial 1 (AIMS-CT1) will examine whether arbaclofen is superior to placebo in improving social function and other secondary outcomes over 16 weeks, along with safety and tolerability profiles.Methods: AIMS-CT1 is an international, multi-site, double-blind, parallel group Phase II randomized clinical trial. It will include 130 males and females aged 5:0–17:11 years, with a diagnosis of ASD and fluent speech. Eligible participants will be randomized on a ratio of 1:1 for a 16-week treatment period. Medication will be titrated over 5 weeks. The primary outcome is the effect on social function from weeks 0 to 16 measured on the Socialization domain of the Vineland Adaptive Behavior Scales, 3rd editionTM. Secondary outcome measures include the CGI–S (Clinical Global Impression–Severity), CGI–I (Clinical Global Impression–Improvement), other areas of adaptive function, social communication and other autism symptoms, co-occurring behavior problems and health-related quality of life. Genetic and electrophysiological markers will be examined as potential stratifiers for treatment response. Exploratory novel digital technologies will also be used to measure change, examining simultaneously the validity of digital biomarkers in natural environments. The safety and tolerability of the drug will also be examined. Our protocol is very closely aligned with a parallel Canadian trial of 90 participants (ARBA Study, US NCT number: NCT03887676) to allow for secondary combined analyses. Outcomes will be compared using both an Intent-to-reat and Per Protocol approach.Discussion: The outcomes of this trial, combined with the parallel Canadian trial, will contribute to the evidence base for medications used to help social difficulties among young autistic individuals; demonstrate the capabilities of the AIMS-2-TRIALS network of academic centers to deliver clinical trials; and support future drug development.Clinical Trial Registration: EudraCT number: 2018-000942-21 and ClinicalTrials.gov registry number: NCT03682978. Currently under protocol v.7.2, dated 20.11.2020.

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.