Valpromide increases amplitude of heart rate circadian rhythm in remitted bipolar and unipolar disorders.A placebo-controlled study

2000 ◽  
Vol 15 (7) ◽  
pp. 424-432 ◽  
Author(s):  
P Lemoine ◽  
J Fondarai ◽  
T Faivre
Keyword(s):  
Heart Rate ◽  
Circadian Rhythm ◽  
Rating Scale ◽  
Small Sample Size ◽  
Bipolar Disorders ◽  
Small Sample ◽  
Sleep Diary ◽  
Controlled Study ◽  
Double Blind ◽  
Sleep Study

The aim of this study was to investigate for the effects of valpromide on heart rate circadian rhythm in remitted recurrent unipolar and bipolar disorders (DSM-III-R). It consisted of a comparative, randomized, double-blind, repeated cross-over study of valpromide versus placebo over four four-week periods. The primary evaluation criteria was heart rate (HR). Secondary criteria comprised motor activity (MA) and the Bech and Rafaelsen mania assessment scale, Horne and Ostberg questionnaire, Montgomery and Asberg depression rating scale, Spiegel questionnaire, a sleep diary, and Clinical Global Impression. Fifteen patients were included, giving 60 one-month periods (30 valpromide periods and 30 placebo periods).Cosinor analysis of HR and MA data revealed a difference in amplitude (P = 0.037, analysis of variance, one-tailed test).The clinical sleep study shows that the duration of sleep was greater with valpromide than with placebo (P = 0.007, one-tailed test). Similarly, evaluation of the quality of sleep by patients themselves showed valpromide to be superior to placebo (P = 0.045, one-tailed test). The results of analysis of the Spiegel questionnaire also confirm the superiority of valpromide over placebo. Safety and compliance were comparable for the active drug and the placebo.In conclusion, the relatively small sample size requires cautious interpretation of this study. Nevertheless, these initial results show a definite effect of valpromide on a biological rhythm that leads one to suppose that it may be effective through a ‘synchronizing’ effect.

Effect of coadministration of propranolol and etodolac (VT-122) plus sorafenib for patients with advanced hepatocellular carcinoma (HCC).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 390-390 ◽  
Author(s):  
Andrew N de la Torre ◽  
Ismael Castaneda ◽  
Aram F. Hezel ◽  
Newell F. Bascomb ◽  
Gouri Shankar Bhattacharyya ◽  
...  
Keyword(s):  
Hepatitis Virus ◽  
Small Sample Size ◽  
Small Sample ◽  
Controlled Study ◽  
Advanced Hepatocellular Carcinoma ◽  
Separate Study ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Duration Of Therapy ◽  
Significant Efficacy

390 Background: Propranolol and etodolac (designated VT-122) target the adrenergic and prostaglandin stress systems activated in HCC. These stress-induced systems are proposed to induce changes in the tumor microenvironment and immune system leading to tumor promotion and immune tolerance. In a separate study, administration of VT-122 prior to sorafenib showed an increase in median overall survival (OS) of 21 months when VT-122 is administered before sorafenib compared to 10 months OS for sorafenib alone. The aim of the current study was to evaluate the effect of administering VT-122 at least 30 days after starting sorafenib. Methods: Patients with HCC receiving sorafenib for at least 30 days were eligible for this double-blind, placebo-controlled study. Patients were randomized to receive sorafenib with either VT-122 or placebo. Patients received therapy for up to 12 months or until treatment failure. VT-122 was administered twice daily. The primary endpoint was duration of therapy (DoT) and the secondary endpoint was OS. Results: Twenty patients were randomized, 11 and 9 patients to the VT122 and placebo arm, respectively. Each arm was balanced with regards to age (mean of 60.4 years), Child Pugh status (9 Child Pugh A, 11 Child Pugh B7), hepatitis virus status (6 HBV and 1 HCV positive) and C-reactive protein (CRP) (20.4 mg/L). VT122 with sorafenib was well tolerated with no unexpected serious adverse events reported. Mean OS was 13.9 months and 9.6 months in the VT-122 and placebo arms, respectively. Mean DoT (unvalidated) was 10.1 months and 7.5 months in the VT-122 and placebo arms, respectively. Conclusions: Co-administration of VT-122 with sorafenib was well tolerated and showed an increase in duration of therapy and OS versus sorafenib alone. The small sample size and number of events precludes the ability to make any significant efficacy conclusions. The increase in survival was not as great as that seen in a separate study in which VT122 was started prior to sorafenib. A further Phase 3 study of VT122 administered prior to sorafenib in patients with HCC is warranted. Clinical trial information: NCT01265576.

scholarly journals Effects of Magnesium Supplementation on Unipolar Depression: A Placebo-Controlled Study and Review of the Importance of Dosing and Magnesium Status in the Therapeutic Response

Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 1014 ◽  
Author(s):  
Beata Ryszewska-Pokraśniewicz ◽  
Anna Mach ◽  
Michał Skalski ◽  
Piotr Januszko ◽  
Zbigniew Wawrzyniak ◽  
...  
Keyword(s):  
Rating Scale ◽  
Antidepressant Treatment ◽  
Small Sample Size ◽  
Serum Magnesium ◽  
Small Sample ◽  
Controlled Study ◽  
Antidepressant Effect ◽  
Double Blind Study ◽  
Magnesium Ions ◽  
Lower Baseline

Animal studies using tests and models have demonstrated that magnesium exerts an antidepressant effect. The literature contains few studies in humans involving attempts to augment antidepressant therapy with magnesium ions. The purpose of our study was to assess the efficacy and safety of antidepressant treatment, in combination with magnesium ions. A total of 37 participants with recurrent depressive disorder who developed a depressive episode were included in this study. As part of this double-blind study, treatment with the antidepressant fluoxetine was accompanied with either magnesium ions (120 mg/day as magnesium aspartate) or placebo. During an 8-week treatment period, each patient was monitored for any clinical abnormalities. Moreover, serum fluoxetine and magnesium levels were measured, and pharmaco-electroencephalography was performed. The fluoxetine + magnesium and fluoxetine + placebo groups showed no significant differences in either Hamilton Depression Rating Scale (HDRS) scores or serum magnesium levels at any stage of treatment. Multivariate statistical analysis of the whole investigated group showed that the following parameters increased the odds of effective treatment: lower baseline HDRS scores, female gender, smoking, and treatment augmentation with magnesium. The parameters that increased the odds of remission were lower baseline HDRS scores, shorter history of disease, the presence of antidepressant-induced changes in the pharmaco-EEG profile at 6 h after treatment, and the fact of receiving treatment augmented with magnesium ions. The limitation of this study is a small sample size.

scholarly journals Effect of Low-dose ColchiciNe on the InciDence of Atrial Fibrillation in Open Heart Surgery Patients: END-AF Low Dose Trial

2020 ◽  
Vol 48 (7) ◽  
pp. 030006052093983
Author(s):  
Ramzi A. Tabbalat ◽  
Imad Alhaddad ◽  
Ayman Hammoudeh ◽  
Yousef S. Khader ◽  
Hassan Abu Khalaf ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Side Effects ◽  
Low Dose ◽  
Heart Surgery ◽  
Small Sample Size ◽  
Open Heart Surgery ◽  
Small Sample ◽  
Controlled Study ◽  
Unique Identifier ◽  
Double Blind

Background Studies using 1 mg of colchicine to prevent postoperative atrial fibrillation (POAF) reported conflicting results. Moreover, colchicine was associated with significant gastrointestinal (GI) side effects. This study examined whether low-dose colchicine effectively prevents POAF and whether low-dose therapy is associated with lower rates of colchicine-induced GI side effects. Methods In this prospective, randomized, double-blind, placebo-controlled study, consecutive adult patients admitted for elective cardiac surgeries randomly received a 1-mg dose of colchicine (n = 81) or placebo (n = 71) orally 12 to 24 hours before surgery followed by a daily dose of 0.5 mg until hospital discharge. The primary efficacy endpoint was the development of at least one episode of POAF of ≥5 minutes. The primary safety endpoint was the development of adverse events, especially diarrhea. Results The in-hospital mortality rate was 3.9%. POAF occurred in 13 patients (16.1%) in the colchicine group and 13 patients (18.3%) in the placebo group (odds ratio 0.85 [95% Confidence Interval = 0.37−1.99]). Diarrhea occurred in two patients in each group and necessitated treatment discontinuation in one patient in each group. Conclusion Low-dose colchicine did not prevent POAF in patients undergoing cardiac surgery. These results should be interpreted cautiously because of the small sample size and early study termination. ClinicalTrials.gov Unique Identifier number: NCT03015831

scholarly journals Double-Blinded Randomized Pilot Clinical Trial Comparing Cognitive Side Effects of Standard Ultra-Brief Right Unilateral ECT to 0.5 A Low Amplitude Seizure Therapy (LAP-ST)

2020 ◽  
Vol 10 (12) ◽  
pp. 979
Author(s):  
Nagy A. Youssef ◽  
William V. McCall ◽  
Dheeraj Ravilla ◽  
Laryssa McCloud ◽  
Peter B. Rosenquist
Keyword(s):  
Clinical Trial ◽  
Side Effects ◽  
Rating Scale ◽  
Small Sample Size ◽  
Bipolar Disorders ◽  
Small Sample ◽  
Treatment Groups ◽  
Double Blinded ◽  
Low Amplitude ◽  
Cognitive Side Effects

Background: Concerns over cognitive side effects (CSE) of electroconvulsive therapy (ECT) still limit its broader usage for treatment-resistant depression (TRD). The objectives of this study were to (1) examine the CSE of Low Amplitude Seizure Therapy (LAP-ST) at 0.5 A compared to Ultra-brief Right Unilateral (UB-RUL) ECT using Time to Reorientation (TRO) as the main acute primary outcome, and (2) to compare effects on depressive symptoms between the two treatment groups. Methods: Participants were referred for ECT, consented for the study, and were randomized to a course of LAP-ST or standard UB-RUL ECT. TRO and depression were measured by the Montgomery-Åsberg Depression Rating Scale (MADRS). Results: Eleven patients consented. Of these, eight with a current major depressive episode (MDE) of unipolar or bipolar disorders were randomized. TRO was faster for the LAP-ST (mean = 6.8 min; SE = 4.9) than standard RUL ECT (mean = 15.5 min; SE = 6.5). Depression improved similarly in the two arms of the study from baseline (MADRS: LAP-ST = 41.0; SE = 2.0, RUL = 39.0; SE = 3.8) to endpoint (MADRS score: LAP-ST = 8.0; SE7.2, RUL = 9.5; SE = 3.8). Conclusions: This pilot, randomized and blinded clinical trial, suggests that the LAP-ST (at 0.5 A) has faster reorientation and possibly lower CSE compared to standard RUL-UB ECT. Caution is advised in interpreting these results due to the small sample size of this pilot study. Thus, future studies with similar design are warranted for replicating these findings.

scholarly journals A double-blind placebo-controlled study of brexpiprazole for the treatment of borderline personality disorder

2021 ◽  
pp. 1-6
Author(s):  
Jon E. Grant ◽  
Stephanie Valle ◽  
Eve Chesivoir ◽  
Dustin Ehsan ◽  
Samuel R. Chamberlain
Keyword(s):  
Borderline Personality Disorder ◽  
Personality Disorder ◽  
Repeated Measures ◽  
Rating Scale ◽  
Safety Data ◽  
Borderline Personality ◽  
Small Sample ◽  
Controlled Study ◽  
Double Blind ◽  
Double Blind Placebo

Background Borderline personality disorder is associated with impaired quality of life and has a number of untoward public health associations. There is no established first-line pharmacological treatment for borderline personality disorder, and available options are not suitable for all individuals. Aims To evaluate brexpiprazole, which has effects on the dopaminergic and serotonergic systems, for the reduction of borderline personality disorder symptoms. Method Eighty adults with borderline personality disorder were recruited for a randomised, double-blind placebo-controlled study. Participants received 12-week treatment with brexpiprazole (1 mg/day for 1 week, then increasing to 2 mg/day) or placebo in a parallel design. The primary efficacy outcome measure was the clinician-rated Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD). Safety data were collected. Effects of active versus placebo treatment were characterised with linear repeated measures models. Results There was a significant interaction between treatment and time on the ZAN-BPD scale (P = 0.0031), solely because of differentiation specifically at week 12. Brexpiprazole was generally well tolerated. Secondary measures did not result in statistically significant differences from placebo. Conclusions Brexpiprazole appears to have some possible effect on borderline personality disorder symptoms, but further studies are needed because of the significant effects evident, specifically at the final time point. These findings also need to be viewed cautiously, given the small sample size, large drop-out rate and robust placebo response.

Safety and Tolerability of Ganoderma lucidum in Healthy Subjects: A Double-Blind Randomized Placebo-Controlled Trial

2007 ◽  
Vol 35 (03) ◽  
pp. 407-414 ◽  
Author(s):  
Sheila M. Wicks ◽  
Robin Tong ◽  
Chong-Zhi Wang ◽  
Michael O'Connor ◽  
Theodore Karrison ◽  
...  
Keyword(s):  
Ganoderma Lucidum ◽  
Small Sample Size ◽  
Controlled Trial ◽  
Statistical Significance ◽  
Blood Chemistry ◽  
Small Sample ◽  
Controlled Study ◽  
Double Blind ◽  
Human Volunteers ◽  
Complete Blood Counts

Ganoderma lucidum is a herbal medicine commonly used in oriental countries as a remedy for treating various medical conditions. In this controlled study, we evaluated the safety and tolerance of oral administration of Ganoderma lucidum in 16 human volunteers who received 2 grams of the extract or placebo twice daily for 10 consecutive days. During the study, information from subjective questionnaires were obtained, electrocardiograms, complete blood counts, blood chemistry analysis and urinalysis were performed. In addition, blood tests reflecting immunity were done. Our data showed that compared to placebo group, no adverse effects were observed after the extract intake. Although there were no obvious changes in CD4, CD8, and CD19 levels after the extract, CD56 cell count increased during the study and returned to baseline 10 days after the herbal intake. However, due to relatively high variability and small sample size, this CD56 increase did not achieve statistical significance, and remains to be re-evaluated in the future. It appears that an additional long-term safety and tolerance trial with herbal dose-escalating design is warranted.

A randomized, double-blind, placebo-controlled study of polyunsaturated fatty acids efficacy in adolescents with anorexia nervosa

2020 ◽  
Vol 36 (2) ◽  
pp. 95-106
Author(s):  
Agnieszka M. Piróg-Balcerzak ◽  
Anna K. Bażyńska ◽  
Katarzyna Biernacka ◽  
Joanna Brągoszewska ◽  
Lidia Popek ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Anorexia Nervosa ◽  
Polyunsaturated Fatty Acids ◽  
Small Sample Size ◽  
Small Sample ◽  
Female Adolescent ◽  
Eating Attitude ◽  
Controlled Study ◽  
Omega 3 ◽  
Eat 26

Objective. Omega–3 polyunsaturated fatty acids (PUFAs) were tested in adolescent depression and in several neurodevelopmental disorders with partial success. Anorexia nervosa (AN) is characterised by deficiencies in fatty food intake and frequent comorbidity, including depressive and cognitive symptoms. Thus supplementation with PUFAs may be beneficial in this group of patients. The aim of the study was to assess whether PUFAs as an add-on treatment is associated with better improvement of body mass index (BMI) and psychopathological symptoms than placebo in patients with AN. Method. 61 female adolescent inpatients with AN were randomly allocated to omega–3 PUFAs supplementation or placebo for 10 weeks. Patients also participated in the behavioural programme and eclectic psychotherapy (treatment as usual, TAU). At baseline and follow-up visits, patients’ BMI and psychopathology were assessed with Clinical Global Impression Scale (CGI), Patient Global Impression Scale (PGI), and Eating Attitude Test (EAT-26). Results. After 10 weeks, both groups showed improvement in all parameters. Improvement in CGI scores was observed greater in placebo vs. PUFA-s group (p = 0.015) while other differences were not statistically significant. Omega–3 PUFAs supplementation appears not to be effective as an add-on treatment in inpatient adolescent girls with anorexia nervosa. Conclusions. The results should be analysed with caution due to small sample size and heterogeneity in TAU. As the TAU turned out to be highly effective, additional therapeutic effect of PUFA might not be visible. Nevertheless, that does not explain the tendency for better improvement in the placebo group.

scholarly journals Treatment of bipolar depression with supraphysiologic doses of levothyroxine: a randomized, placebo-controlled study of comorbid anxiety symptoms

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Maximilian Pilhatsch ◽  
Thomas J Stamm ◽  
Petra Stahl ◽  
Ute Lewitzka ◽  
Anne Berghöfer ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Phenotypic Expression ◽  
Anxiety Symptoms ◽  
Controlled Study ◽  
Double Blind ◽  
Comorbid Anxiety ◽  
Depressed Patients ◽  
Depressive Episodes

Abstract Background Symptoms of anxiety co-occur in a variety of disorders including in depressive episodes of bipolar disorder and in patients with thyrotoxicosis. Treatment of refractory bipolar disorder with supraphysiologic doses of levothyroxine (L-T4) has been shown to improve the phenotypic expression of the disorder and is associated with an increase of circulating thyroid hormones. However, it might be associated with somatic and mental adverse effects. Here we report the investigation of the influence of treatment with supraphysiologic doses of L-T4 on symptoms of anxiety in patients with refractory bipolar depression. Methods Post-hoc analysis from a 6-week, multi-center, randomized, double-blind, placebo-controlled study of the effects of supraphysiologic L-T4 treatment on anxiety symptoms in bipolar depression. Anxiety symptoms were measured weekly with the Hamilton anxiety/somatization factor (HASF) score of the Hamilton Depression Rating Scale (HAMD) and the State- and Trait Anxiety Inventory (STAI). Results Treatment of both groups was associated with a significant reduction in anxiety symptoms (p < 0.001) with no statistical difference between groups (LT-4: from 5.9 (SD = 2.0) at baseline to 3.7 (SD = 2.4) at study end; placebo: from 6.1 (SD = 2.4) at baseline to 4.4 (SD = 2.8) at study end; p = 0.717). Severity of anxiety at baseline did not show a statistically significant correlation to the antidepressive effect of treatment with supraphysiologic doses of L-T4 (p = 0.811). Gender did not show an influence on the reduction of anxiety symptoms (females: from 5.6 (SD = 1.7) at baseline to 3.5 (SD = 2.4) at study end; males: from 6.1 (SD = 2.3) at baseline to 4.0 (SD = 2.4) at study end; p = 0.877). Conclusions This study failed to detect a difference in change of anxiety between bipolar depressed patients treated with supraphysiologic doses of L-T4 or placebo. Comorbid anxiety symptoms should not be considered a limitation for the administration of supraphysiologic doses of L-T4 refractory bipolar depressed patients. Trial registration ClinicalTrials, ClinicalTrials.gov identifier: NCT01528839. Registered 2 June 2012—Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT01528839

Double-Blind and Placebo-Controlled Study of Lithium for Adolescent Bipolar Disorders With Secondary Substance Dependency

1998 ◽  
Vol 37 (2) ◽  
pp. 171-178 ◽  
Author(s):  
BARBARA GELLER ◽  
THOMAS B. COOPER ◽  
KAI SUN ◽  
BETSY ZIMERMAN ◽  
JEANNE FRAZIER ◽  
...  
Keyword(s):  
Bipolar Disorders ◽  
Controlled Study ◽  
Double Blind ◽  
Secondary Substance

Modulation of Remifentanil-induced Analgesia and Postinfusion Hyperalgesia by Parecoxib in Humans

2006 ◽  
Vol 105 (5) ◽  
pp. 1016-1023 ◽  
Author(s):  
Andreas Tröster ◽  
Ruth Sittl ◽  
Boris Singler ◽  
Martin Schmelz ◽  
Jürgen Schüttler ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Rating Scale ◽  
Control Level ◽  
Numeric Rating Scale ◽  
Cyclooxygenase 2 ◽  
Controlled Study ◽  
Double Blind ◽  
Antinociceptive Effects ◽  
Current Densities ◽  
Mu Opioids

Background Numerous experimental and clinical studies suggest that brief opioid exposure can enhance pain sensitivity. It is suggested that spinal cyclooxygenase activity may contribute to the development and expression of opioid tolerance. The aim of the investigation was to determine analgesic and antihyperalgesic properties of the cyclooxygenase-2 inhibitor parecoxib on remifentanil-induced hypersensitivity in humans. Methods Fifteen healthy male volunteers were enrolled in this randomized, double-blind, placebo-controlled study in a crossover design. Transcutaneous electrical stimulation at high current densities was used to induce spontaneous acute pain (numeric rating scale 6 of 10) and stable areas of pinprick hyperalgesia. Pain intensities and areas of hyperalgesia were assessed before, during, and after a 30-min intravenous infusion of remifentanil (0.1 microg x kg x min) or placebo (saline). Parecoxib (40 mg) was administered intravenously either with onset of electrical stimulation (preventive) or in parallel to the remifentanil infusion. Results Remifentanil reduced pain and mechanical hyperalgesia during the infusion, but upon withdrawal, pain and hyperalgesia increased significantly above control level. Preventive administration of parecoxib led to an amplification of remifentanil-induced antinociceptive effects during the infusion (71.3 +/- 7 vs. 46.4 +/- 17% of control) and significantly diminished the hyperalgesic response after withdrawal. In contrast, parallel administration of parecoxib did not show any modulatory effects on remifentanil-induced hyperalgesia. Conclusion The results confirm clinically relevant interaction of mu opioids and prostaglandins in humans. Adequate timing seems to be of particular importance for the antihyperalgesic effect of cyclooxygenase-2 inhibitors.

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