Effect of Adding l -Carnitine to Risperidone on Behavioral, Cognitive, Social, and Physical Symptoms in Children and Adolescents With Autism: A Randomized Double-Blinded Placebo-Controlled Clinical Trial.

OBJECTIVES: The present research aimed to evaluate the effect of adding l -carnitine to risperidone in treating children and adolescents with autism spectrum disorder (ASD). METHODS: In this randomized controlled clinical trial study, 50 ASD children and adolescents were divided into 2 groups: those receiving l -carnitine and risperidone (n = 25) and those receiving placebo and risperidone (n = 25). Treatment continued for 8 weeks, and participants were assessed at the beginning of the study, in the fourth and eighth weeks, by the Aberrant Behavior Checklist (ABC). RESULTS: l -Carnitine add-on therapy reduced the scores of total ABC and subscales of restlessness, lethargy and social isolation, stereotypic behavior, and inappropriate speech at weeks 4 and 8. There was a significant difference between the 2 groups in the score of total ABC and subscale of lethargy and social isolation. CONCLUSIONS: According to the present study, adding l -carnitine to risperidone improves ASD symptoms.

Term Neonatal Outcomes after Maternal Magnesium Sulfate Treatment for Seizure Prophylaxis.

OBJECTIVE: This study aimed to evaluate term neonatal outcomes after maternal magnesium sulfate (MgSO4) treatment for seizure prophylaxis. STUDY DESIGN: This was a single-site retrospective cohort study of all women with term singleton gestation requiring MgSO4 treatment for seizure prophylaxis and their respective neonatal outcomes from January 2013 through December 2020. Our primary outcome was neonatal intensive care unit (NICU) admission. We compared outcomes between women treated with MgSO4 for 24 hours or more and women treated with MgSO4 for less than 24 hours prior to delivery. Multivariable logistic regression was performed to calculate adjusted odds ratio (aOR) and 95% confidence interval (95% CI), controlling for variables with a p < 0.05 based on bivariable analysis. RESULTS: Of 834 women analyzed, 173 (20.7%) neonates were admitted to the NICU. Women treated with MgSO4 for 24 hours or more compared with women treated with MgSO4 for less than 24 hours were more likely to have neonates admitted to the NICU during their hospitalization (27.3 vs. 18.9%; p = 0.01), neonates requiring immediate NICU admission (24.6 vs. 18.3%; p < 0.01), and NICU admission for neonatal lethargy. After adjusting for covariates, only NICU admission due to neonatal lethargy remained statistically significant (aOR: 4.78 [95% CI: 1.50-15.21]). CONCLUSION: Prolonged MgSO4 treatment for 24 hours or more was associated with increased odds of term NICU admission due to neonatal lethargy. KEY POINTS: · NICU admission rose with longer magnesium treatment.. · Nulliparous patients had more magnesium sulfate exposure.. · Obese patients had longer magnesium sulfate exposure..

Symptom Dimension of Interest-Activity Indicates Need for Aripiprazole Augmentation of Escitalopram in Major Depressive Disorder: A CAN-BIND-1 Report.

OBJECTIVE: Differential predictors of response to alternative treatment options are needed to improve the outcomes in major depressive disorder. The symptom dimension comprising loss of interest and reduced activity has been reported as a predictor of poor outcome of treatment with antidepressants. We hypothesized that augmentation with partial dopamine agonist aripiprazole will be effective for individuals with pronounced interest-activity symptoms. METHODS: We tested the hypothesis in the 2-phase Canadian Biomarker Integration Network in Depression trial 1 (CAN-BIND-1). All participants had a primary diagnosis of major depressive disorder confirmed with the Mini-International Neuropsychiatric Interview. In phase 1, 188 individuals received escitalopram monotherapy 10-20 mg daily for 8 weeks. In phase 2, nonresponders received augmentation with aripiprazole 2-10 mg daily while responders continued escitalopram monotherapy for another 8 weeks. Outcomes were measured with the Montgomery-Åsberg Depression Rating Scale (MADRS) every 2 weeks. Effects of baseline interest-activity symptoms on outcomes were tested in repeated-measures mixed-effects models. RESULTS: Higher baseline interest-activity score (indicative of more severe loss of interest and reduction in activity) predicted worse outcome of escitalopram monotherapy in phase 1 (b = 1.75; 95% CI, 0.45 to 3.05; P = .009), but the association disappeared with the augmentation option in phase 2 (b = -0.19; 95% CI, -1.30 to 0.92; P = .739). A significant interaction between the baseline interest-activity score and aripiprazole reflected the opposite direction of the relationship between baseline interest-activity score and degree of improvement with escitalopram monotherapy versus aripiprazole augmentation (b = -1.60; 95% CI, -2.35 to -0.84; P < .001). CONCLUSIONS: Individuals with prominent loss of interest and reduction in activity benefit less from escitalopram monotherapy and more from aripiprazole augmentation. Future trials may test the benefits of early prodopaminergic augmentation guided by interest-activity symptoms. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01655706.

[Glucocorticoids and androgens for treatment of tiredness and weakness in palliative care patients : a systematic review]. / Glukokortikoide und androgene zur behandlung von müdigkeit und schwäche bei palliativpatienten : eine systematische übersichtsarbeit.

BACKGROUND: The therapy of tiredness, weakness and fatigue in palliative care patients is of growing interest. Glucocorticoids and androgens are habitually mentioned drugs for treatment. In this review evidence for glucocorticoids and androgens for these indications in palliative care patients are presented. MATERIALS AND METHODS: A systematic search of PubMed and Embase for studies on glucocorticoids and androgens for fatigue, asthenia, sedation, tiredness, weakness, exhaustion, cachexia, drowsiness and wasting in palliative care was carried out in August 2011. Furthermore, the Cochrane Library, references from the literature and leading textbooks were also searched. Study information was entered in a standardized extraction sheet. By a categorization of studies five endpoints were distinguished: fatigue, strength/weakness, tiredness, well being/quality of life and energy/activity/performance. RESULTS: A total of 11 controlled studies with glucocorticoids and 13 controlled studies with androgens were included. In addition four uncontrolled studies, two case series and two surveys with glucocorticoids as well as six uncontrolled studies and one case series with androgen treatment were analyzed. All controlled trials of glucocorticoids were performed in cancer patients and all but one controlled trial of androgens in patients with HIV/AIDS. Glucocorticoids improved quality of life but results for changes of fatigue and weakness were inconsistent. Tiredness and energy were not improved. Androgens had a positive effect on fatigue and quality of life and showed variable effects on weakness. Androgens did not improve energy. Side effects were frequently documented but only rarely resulted in discontinuation of therapy. CONCLUSION: With the existing evidence no general recommendation for glucocorticoid and androgen use in tiredness and weakness in palliative care patients can be given; however, glucocorticoids in cancer patients and androgens in HIV positive-patients can be used in an individual trial for improving patient quality of life. The use in patients suffering from other disease entities should be evaluated in randomized controlled trials with a similar setting. The English full text version of this article will be available in SpringerLink as of November 2012 (under "Supplemental").

Inflammation-induced lethargy is mediated by suppression of orexin neuron activity.

In response to illness, animals subvert normal homeostasis and divert their energy utilization to fight infection. An important and unexplored feature of this response is the suppression of physical activity and foraging behavior in the setting of negative energy balance. Inflammatory signaling in the hypothalamus mediates the febrile and anorectic responses to disease, but the mechanism by which locomotor activity (LMA) is suppressed has not been described. Lateral hypothalamic orexin (Ox) neurons link energy status with LMA, and deficiencies in Ox signaling lead to hypoactivity and hypophagia. In the present work, we examine the effect of endotoxin-induced inflammation on Ox neuron biology and LMA in rats. Our results demonstrate a vital role for diminished Ox signaling in mediating inflammation-induced lethargy. This work defines a specific population of inflammation-sensitive, arousal-associated Ox neurons and identifies a proximal neural target for inflammatory signaling to Ox neurons, while eliminating several others.

Methylphenidate for the treatment of apathy in Alzheimer disease: prediction of response using dextroamphetamine challenge.

Apathy is a common behavioral symptom of Alzheimer's disease (AD), being present in up to 70% of patients. Apathy in AD and non-AD populations has been associated with dysfunction in the dopaminergic brain reward system, suggesting that pharmacotherapeutic targeting of this system may be an effective treatment for apathy in AD. We therefore performed a randomized, double-blind, placebo-controlled crossover trial of methylphenidate in a sample of 13 apathetic AD patients (6 men, 7 women; age mean 77.9 years [SD, 7.8 years]; Mini Mental Status Examination score, 19.9 [SD, 4.7]). Patients were treated with methylphenidate (10 mg PO twice a day) or an identical placebo in two 2-week phases separated by a 1-week placebo washout. All patients participated in a dextroamphetamine challenge test (one 10-mg oral dose) before treatment with methylphenidate to gauge the functional integrity of the dopamine brain reward system. Overall, patients demonstrated greater improvement with methylphenidate compared with placebo according to Apathy Evaluation Scale total change scores (end of treatment - baseline: Wilcoxon Z = -2.00; P = 0.047). However, a significantly greater proportion of patients experienced at least 1 adverse event with methylphenidate compared with placebo (3 vs 1; chi = 4.33, P = 0.038). Two patients experienced serious adverse events with methylphenidate, consisting of delusions, agitation, anger, irritability, and insomnia, which resolved upon discontinuation of the medication. Response to methylphenidate was associated with increases in inattention on a continuous performance task after dextroamphetamine challenge. Psychostimulants may be effective in treating features of apathy in AD, and dopaminergic changes may predict response.