scholarly journals One-week escitalopram intake shifts excitation-inhibition balance in the healthy female brain

2021 ◽  
Author(s):  
Rachel G. Zsido ◽  
Eóin N. Molloy ◽  
Elena Cesnaite ◽  
Gergana Zheleva ◽  
Nathalie Beinhölzl ◽  
...  
Keyword(s):  
Single Dose ◽  
Steady State ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Double Blind Study ◽  
Healthy Human ◽  
Double Blind ◽  
Female Brain ◽  
Healthy Female ◽  
Cortical Excitation ◽  
Relationship Of

Background: Neural health relies on cortical excitation-inhibition balance (EIB), with disrupted EIB underlying circuit dysfunction in several neuropsychiatric disorders. Previous research suggests links between increased cortical excitation and neuroplasticity induced by selective serotonin reuptake inhibitors (SSRIs). Whether there are modulations of EIB following SSRI-administration in the healthy human brain, however, remains unclear. To this end, we assessed changes in EIB following longitudinal escitalopram-intake. Methods: In a randomized, double-blind study protocol, a sample of 59 healthy female individuals on oral contraceptives underwent three resting-state electroencephalography recordings after daily administration of 20 mg escitalopram (n = 28) or placebo (n = 31) at baseline, after single dose, and after 1 week (steady state).We assessed 1/f slope of the power spectrum, a marker of EIB, compared individual trajectories of 1/f slope changes contrasting single dose and 1-week drug intake, and tested the relationship of escitalopram plasma levels and cortical excitatory and inhibitory balance shifts. Results: Escitalopram-intake associated with decreased 1/f slope, indicating an EIB shift in favor of excitation. Furthermore, 1/f slope at baseline and after single dose of escitalopram predicted 1/f slope at steady state. Higher plasma escitalopram levels at single dose associated with better maintenance of these EIB changes throughout the drug administration week. Conclusions: Characterizing changes in 1/f slope during longitudinal SSRI-intake in healthy female individuals, we show that escitalopram shifted EIB in favor of excitation. These findings demonstrate the potential for 1/f slope to predict individual cortical responsivity to SSRIs and widen the neuroimaging lens by testing an interventional psychopharmacological design in a clearly-defined endocrinological state.

Single dose oral ranitidine improves MRCP image quality: a double-blind study

2007 ◽  
Vol 62 (1) ◽  
pp. 53-57 ◽  
Author(s):  
M.T. Bowes ◽  
D.F. Martin ◽  
A. Melling ◽  
D. Roberts ◽  
H.-U. Laasch ◽  
...  
Keyword(s):  
Single Dose ◽  
Image Quality ◽  
Blind Study ◽  
Double Blind Study ◽  
Double Blind ◽  
Dose Oral

Consumption by Healthy Adults of Pasteurized Milk with a High Concentration of Bacillus cereus: A Double-Blind Study

1996 ◽  
Vol 59 (7) ◽  
pp. 723-726 ◽  
Author(s):  
LEO P. M. LANGEVELD ◽  
WILLEM A. VAN SPRONSEN ◽  
EMERENTIA C. H. VAN BERESTEIJN ◽  
SERVÉ H. W. NOTERMANS
Keyword(s):  
Bacillus Cereus ◽  
Healthy Adults ◽  
Double Blind Study ◽  
High Concentration ◽  
Healthy Human ◽  
Double Blind ◽  
Pasteurized Milk ◽  
Human Volunteers ◽  
Pure Cultures ◽  
Gastrointestinal Complaints

A double-blind experiment with 34 healthy human volunteers, aged between 20 and 60 years, was conducted to obtain information about the allowable concentration of B. cereus in pasteurized milk. During a period of 3 weeks the subjects were exposed to B. cereus naturally present in pasteurized milk following storage for 3 to 14 days at 7.5°C. Of 259 milk exposures, gastrointestinal complaints were observed in 18 cases. According to total numbers of B. cereus ingested per exposure the complaints per number of exposures were distributed as follows: < 106: 5 in 132; 106 to 107: 2 in 32; 107 to 108 : 2 in 26; and > 108: 9 in 69. Symptoms, however, were not typical of those caused by B. cereus. There was a weak significance (P ≤ 0.1) for symptoms when > 108 B. cereus cells were ingested. Milk with 106 to 107 B. cereus cells per ml showed a very low diarrheal enterotoxin titer. Pure cultures of B. cereus strains isolated from samples with high B. cereus concentrations also showed a low production of enterotoxin. It can be concluded that for healthy adults the probability of become diseased from cold-stored pasteurized milk is small. From the results no evidence is obtained that B. cereus concentrations less than 105/ml will cause intoxication.

Prediction of steady-state occupancy of the serotonin transporter based on single-dose occupancy: A [11C]DASB pet study

2011 ◽  
Vol 26 (S2) ◽  
pp. 929-929 ◽  
Author(s):  
A.S. Höflich ◽  
C. Philippe ◽  
M. Savli ◽  
P. Baldinger ◽  
G.S. Kranz ◽  
...  
Keyword(s):  
Single Dose ◽  
Steady State ◽  
Serotonin Transporter ◽  
Oral Treatment ◽  
Term Treatment ◽  
Linear Regression Models ◽  
Double Blind ◽  
Long Term Treatment ◽  
Subcortical Regions ◽  
The Relationship

IntroductionClinical studies point toward a potential role of the serotonin transporter (SERT) binding as a predictor of clinical outcome in the treatment of depression. After long-term treatment with clinical doses of SSRIs the expected SERT occupancy is about 80%. Here, we were interested to investigate the relationship of SERT occupancy values between short- and longterm treatment.ObjectivesTo test if the SERT occupancy at steady-state can be predicted based on the single dose occupancy by escitalopram (S-citalopram) or citalopram (racemate of S-citalopram and R-citalopram).Methods18 patients with major depressive disorder received either escitalpram (10 mg/d) or citalopram (20 mg/d) in a double-blind, randomized, longitudinal study. They underwent three PET scans using the radioligand [11C]DASB: PET1 baseline, PET2 6 hours after first drug intake and PET3 after three weeks of daily oral treatment. Occupancy of SERT was quantified in six subcortical regions: thalamus, N. caudatus, putamen, mibrain, dorsal raphe and median raphe nuclei. Data was analyzed by means of multiple linear regression models corrected for baseline SERT availability values using SPSS 15.0.ResultsSingle dose occupancy of the SERT significantly predicted steady-state occupancy after three weeks in three regions: thalamus (r2 = 0.45, p = 0.009), N. caudatus (r2 = 0.4, p = 0.006) and putamen (r2 = 0.43, p = 0.005). Other regions did not show significant relationships.ConclusionsIn this study we demonstrated that single-dose occupancy in SERT rich regions such as thalamus, N. caudatus and the putamen could serve as reliable predictors for steady-state occupancy. However, a linear model failed to explain the relationship in regions known for serotonergic cell origin.

scholarly journals Comparison of Ondansetron with Gabapentin for prevention of intrathecal morphine induced pruritus

2019 ◽  
Vol 2 (3) ◽  
pp. 142-148
Author(s):  
Rohini Sigdel ◽  
Anil Shrestha ◽  
Roshana Amatya
Keyword(s):  
Single Dose ◽  
Intrathecal Morphine ◽  
Double Blind Study ◽  
Physical Status ◽  
Hyperbaric Bupivacaine ◽  
Double Blind ◽  
Subarachnoid Block ◽  
Significant Difference ◽  
Group 2 ◽  
To Receive

Background: Ondansetron has been used successfully for prophylaxis and treatment of intrathecal morphine induced pruritus. Gabapentin has anxiolytic, antiemetic, antipruritic effects and has also been shown to potentiate the analgesic effect of intrathecally or epidurally administered opioids. Materials and method: We compared the effectiveness of oral gabapentin with intravenous ondansetron to prevent incidence of intrathecal morphine induced pruritus. In a prospective, double-blind study, sixty patients aged 18-65 years with ASA physical status I and II undergoing surgery under subarachnoid block were randomized to receive placebo tablets (ondansetron group) or gabapentin 1200 mg (gabapentin group) 2 hours before surgery. Patients receiving placebo tablets received 8 mg of intravenous ondansetron and those receiving gabapentin received 4 ml of intravenous normal saline just prior to subarachnoid block with 3 ml of 0.5% hyperbaric bupivacaine plus 0.2 mg morphine. The incidence, onset, severity, location of pruritus and incidence of side effects were studied for next 24 hours. Results: The overall incidence of pruritus was 48.3%. The incidence, severity, location of pruritus was comparable between the two groups. There was significant difference between the onset of pruritus between groups (p=0.009). The incidence and grade of nausea vomiting, requirement of intraoperative sedation was comparable between groups. The incidence of urinary retention was significantly high in gabapentin group (p=0.020). Respiratory depression was observed in one patient. Conclusion: A single dose of 1200 mg oral gabapentin 2 hours before, is as effective as prophylactic intravenous ondansetron 8 mg for prevention of intrathecal morphine induced pruritus.

scholarly journals Citalopram plus low-dose pipamperone versus citalopram plus placebo in patients with major depressive disorder: an 8-week, double-blind, randomized study on magnitude and timing of clinical response

2011 ◽  
Vol 41 (10) ◽  
pp. 2089-2097 ◽  
Author(s):  
A. G. Wade ◽  
G. M. Crawford ◽  
C. B. Nemeroff ◽  
A. F. Schatzberg ◽  
T. Schlaepfer ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Therapeutic Effect ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Receptor Activation ◽  
Double Blind Study ◽  
Major Depressive ◽  
Double Blind ◽  
Madrs Score ◽  
Antidepressant Effects

BackgroundSelective serotonin reuptake inhibitors take several weeks to achieve their full antidepressant effects. Post-synaptic 5-HT2A receptor activation is thought to be involved in this delayed therapeutic effect. Pipamperone acts as a highly selective 5-HT2A/D4 antagonist when administered in low doses. The purpose of this study was to compare citalopram 40 mg once daily plus pipamperone 5 mg twice daily (PipCit) versus citalopram plus placebo twice daily for magnitude and onset of therapeutic effect.MethodAn 8-week, randomized, double-blind study in patients with major depressive disorder was carried out.ResultsThe study population comprised 165 patients (citalopram and placebo, n=82; PipCit, n=83) with a mean baseline Montgomery–Asberg Depression Rating Scale (MADRS) score of 32.6 (s.d.=5.5). In the first 4 weeks, more citalopram and placebo than PipCit patients discontinued treatment (18% v. 4%, respectively, p=0.003). PipCit patients had significantly greater improvement in MADRS score at week 1 [observed cases (OC), p=0.021; last observation carried forward (LOCF), p=0.007] and week 4 (LOCF, p=0.025) but not at week 8 compared with citalopram and placebo patients. Significant differences in MADRS scores favoured PipCit in reduced sleep, reduced appetite, concentration difficulties and pessimistic thoughts. Mean Clinical Global Impression–Improvement scores were significantly improved after 1 week of PipCit compared with citalopram and placebo (OC and LOCF, p=0.002).ConclusionsAlthough the MADRS score from baseline to 8 weeks did not differ between groups, PipCit provided superior antidepressant effects and fewer discontinuations compared with citalopram and placebo during the first 4 weeks of treatment, especially in the first week.

scholarly journals F reticulocyte response in sickle cell anemia treated with recombinant human erythropoietin: a double-blind study

Blood ◽  
1993 ◽  
Vol 81 (1) ◽  
pp. 9-14 ◽  
Author(s):  
RL Nagel ◽  
E Vichinsky ◽  
M Shah ◽  
R Johnson ◽  
E Spadacino ◽  
...  
Keyword(s):  
Steady State ◽  
Side Effects ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Recombinant Human Erythropoietin ◽  
The Other ◽  
Double Blind Study ◽  
Double Blind ◽  
Human Erythropoietin ◽  
Iron Deficient

Abstract Studies on baboons and preliminary observations in three patients with sickle cell anemia (SS) suggested that high doses of pulse administered recombinant human erythropoietin (rHuEPO) stimulate F-reticulocyte production. We now report on the administration of rHuEPO in a double- blind format to ascertain frequency of response and potential precipitation of side effects. Ten patients were enrolled, but one was discontinued due to the indication of a blood transfusion. Of the other nine, five received rHuEPO in escalating doses (from 400 to 1,500 U per kg twice daily [BID] per week), alternating with a placebo, in blinded fashion. The second group, consisting of four patients, followed an identical protocol (except starting dose was 1,000 U/Kg, BID per week) and were iron supplemented during treatment. The criterion of response was a transient doubling (as a minimum) of the steady-state F- reticulocyte level. We found that none of the five patients in the first group responded to rHuEPO, and two of them became iron deficient, as judged by a significant decrease in ferritin. Of the second group, four patients responded with F-reticulocyte increases. In three patients, open label administration of rHuEPO confirmed the effect. We observed seven painful episodes during this study, two during the EPO administration and five during the placebo arm. Three patients were phlebotomized because the hemoglobin level increased 1.5 g/dL more than steady-state levels. Of the six patients followed-up by percent dense cell determinations, one exhibited increased levels during periods of the treatment, whereas the other five showed no change. No anti-rHuEPO antibodies were detected. We conclude that rHuEPO can stimulate F- reticulocyte response in some patients with sickle cell anemia, without apparent negative clinical side effects. The state of iron stores may be critical. Whether higher doses of rHuEPO and/or a different regimen might induce sustained F cells and fetal hemoglobin increases remains to be determined.

Safety of intravenous (IV) NEPA and oral NEPA for prevention of CINV in patients (pts) with breast cancer (BC) receiving anthracycline/cyclophosphamide (AC) chemotherapy (CT).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11594-11594
Author(s):  
Lee S. Schwartzberg ◽  
Daniel Voisin ◽  
Giada Rizzi ◽  
Kamal Patel ◽  
Matti S. Aapro
Keyword(s):  
Single Dose ◽  
Safety Evaluation ◽  
Complete Response ◽  
Primary Objective ◽  
Double Blind Study ◽  
Infusion Site ◽  
Double Blind ◽  
Antiemetic Agent ◽  
Pivotal Study ◽  
Safety Population

11594 Background: NEPA, a combination antiemetic agent [NK1 receptor antagonist (RA) netupitant (oral) or fosnetupitant (IV) + 5-HT3RA palonosetron] offers 5-day CINV prevention with a single-dose. Unlike other IV NK1RAs, the fosnetupitant solution does not require a surfactant, emulsifier, or solubility enhancer and contains no allergenic excipients. In a Phase 3 study in pts receiving cisplatin-based CT, there were no infusion site or anaphylactic reactions related to IV NEPA. In contrast, hypersensitivity reactions and anaphylaxis have been reported with IV aprepitant, fosaprepitant and rolapitant, with the highest rate (35%) for fosaprepitant in the AC setting. This study (NCT03403712) evaluates the safety of IV NEPA in BC pts receiving repeat cycles of AC CT. Methods: This was a Phase 3b, double-blind study in females with BC naïve to highly/moderately emetogenic CT. Pts were randomized 1:1 to receive a single 30-min infusion of IV NEPA or a single oral NEPA capsule on Day 1, prior to AC. Oral dexamethasone was also given to all patients before CT. The primary objective was a safety evaluation of IV NEPA based primarily on treatment-emergent adverse events (TEAEs). No formal between groups statistical comparison was planned. Results: 402 pts were treated with IV NEPA or oral NEPA and included in the safety population. The AE profiles were similar for the two groups; cycle 1 results are reported (Table). Comparable complete response (no emesis, no rescue) rates were seen during the cycle 1 overall phase (0-120h) (73.0% IV NEPA, 77.2% oral NEPA). Conclusions: There were no infusion-site AEs related to IV NEPA and no anaphylaxis reported for either formulation. Consistent with the pivotal study, IV NEPA is safe and effective in pts receiving AC. As a simplified single-dose formulation, IV NEPA may be better tolerated than other NK1 RAs. Clinical trial information: NCT03403712. [Table: see text]

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