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 Acute response to cholinergic challenge predicts long-term response to galantamine treatment in patients with Alzheimer's Disease

2021 ◽  
Author(s):  
Anne Catrien Baakman ◽  
Carmen Gavan ◽  
Lotte Van Doeselaar ◽  
Marieke de Kam ◽  
Karen Broekhuizen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Single Dose ◽  
Term Treatment ◽  
Subsequent Treatment ◽  
Analysis Of Covariance ◽  
Open Label ◽  
Double Blind ◽  
Long Term Treatment

Cholinesterase inhibitors have been shown to improve cognitive functioning in patients with Alzheimer’s Disease (AD), but are associated with side effects and only 20-40% of the patients clinically improve. In this study, we aimed to investigate the acute pharmacodynamic (PD) effects of a single dose of galantamine on CNS functioning in mild to moderate AD patients and its potential to predict long-term treatment response. This study consisted of a challenge phase, in which a single dose of 16 mg galantamine was administered to 50 mild to moderate AD patients in a double-blind, placebo-controlled cross-over fashion. Acute PD effects were monitored with use of a CNS test battery. In the subsequent treatment phase of the study, patients were treated with open-label galantamine according to regular care. After 6 months of galantamine treatment, patients were categorized as either responder or as non-responder based on their MMSE, NPI and DAD scores. An analysis of covariance was performed to study the difference in acute PD effects between responders and non-responders. Acute decreases of absolute frontal alpha (-20.4; 95%CI=-31.6,-7.47; p=.0046), beta (-15.7; 95% CI=-28.3,-0.93; p=.0390) and theta (-25.9; 95%CI=-38.4,-10.9; p=.0024) EEG parameters and of relative frontal theta power (-3.27%; 95%CI=-5.96,-0.58; p=.0187) on EEG after a single dose administration of galantamine significantly distinguished long-term treatment responders (n=11) from non-responders (n=32) after 6 months. This study demonstrates that patients who demonstrate a reduction in EEG power in the alpha and theta frequency after a single administration of galantamine 16 mg will most likely respond to treatment.

Cognitive Treatment for OCD

2012 ◽  
Author(s):  
Maureen L. Whittal ◽  
Melisa Robichaud
Keyword(s):  
Term Treatment ◽  
Future Directions ◽  
Cognitive Treatment ◽  
Long Term Treatment ◽  
Inflated Responsibility ◽  
And Control ◽  
The Relationship ◽  
Control Of Thoughts

The cornerstone of cognitive treatment (CT) for OCD is based upon the knowledge that unwanted intrusions are essentially a universal experience. As such, it is not the presence of the intrusion that is problematic but rather the associated meaning or interpretation. Treatment is flexible, depending upon the nature of the appraisals and beliefs, but can include strategies focused on inflated responsibility and overestimation of threat, importance and control of thoughts, and the need for perfectionism and certainty. The role of concealment and the relationship to personal values are important maintaining and etiological factors. The short-term and long-term treatment outcome is reviewed, along with predictors of treatment response and mechanisms of action, and the chapter concludes with future directions regarding CT for OCD.

New data on the use of lithium, divalproate, and lamotrigine in rapid cycling bipolar disorder

2005 ◽  
Vol 20 (2) ◽  
pp. 92-95 ◽  
Author(s):  
JR Calabrese ◽  
DJ Rapport ◽  
EA Youngstrom ◽  
K. Jackson ◽  
S. Bilali ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Unmet Need ◽  
Depressive Illness ◽  
Term Treatment ◽  
Rapid Cycling ◽  
Double Blind ◽  
Parallel Group Design ◽  
Parallel Group ◽  
Long Term Treatment ◽  
Current Therapies

AbstractThe rapid cycling variant of bipolar disorder is defined as the occurrence of four periods of either manic or depressive illness within 12 months. Patients suffering from this variant of bipolar disorder have an unmet need for effective treatment. This review examines two major studies in an attempt to update understanding of the current therapies available to treat rapid cycling patients. The first trial compares lamotrigine versus placebo in 182 patients studied for 6 months. The second is a recently completed, 20-month trial comparing divalproate and lithium in 60 patients. Both trials had a double-blind, randomized parallel-group design. The data from the latter study indicate that there are no large differences in efficacy between lithium and divalproate in the long-term treatment of rapid cycling bipolar disorder. In addition, lamotrigine has the potential to complement the spectrum of lithium and divalproate through its greater efficacy for depressive symptoms.

Free fatty acids normalize a rosiglitazone-induced visfatin release

2006 ◽  
Vol 291 (5) ◽  
pp. E885-E890 ◽  
Author(s):  
Dominik G. Haider ◽  
Friedrich Mittermayer ◽  
Georg Schaller ◽  
Michaela Artwohl ◽  
Sabina M. Baumgartner-Parzer ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Term Treatment ◽  
Double Blind ◽  
Lipid Infusion ◽  
Major Mechanism ◽  
Insulin Mimetic ◽  
Long Term Treatment ◽  
Plasma Ffa

The detrimental effect of elevated free fatty acids (FFAs) on insulin sensitivity can be improved by thiazolidinediones (TZDs) in patients with type 2 diabetes mellitus. It is unknown whether this salutary action of TZD is associated with altered release of the insulin-mimetic adipocytokine visfatin. In this study, we investigated whether visfatin concentrations are altered by FFA and TZD treatment. In a randomized, double-blind, placebo-controlled, parallel-group study 16 healthy volunteers received an infusion of triglycerides/heparin to increase plasma FFA after 3 wk of treatment with rosiglitazone (8 mg/day, n = 8) or placebo ( n = 8), and circulating plasma visfatin was measured. As a corollary, human adipocytes were incubated with synthetic fatty acids and rosiglitazone to assess visfatin release in vitro. The results were that rosiglitazone treatment increased systemic plasma visfatin concentrations from 0.6 ± 0.1 to 1.7 ± 0.2 ng/ml ( P < 0.01). Lipid infusion caused a marked elevation of plasma FFA but had no effect on circulating visfatin in controls. In contrast, elevated visfatin concentrations in subjects receiving rosiglitazone were normalized by lipid infusion. In isolated adipocytes, visfatin was released into supernatant medium by acute addition and long-term treatment of rosiglitazone. This secretion was blocked by synthetic fatty acids and by inhibition of phosphatidylinositol 3-kinase or Akt. In conclusion, release of the insulin-mimetic visfatin may represent a major mechanism of metabolic TZD action. The presence of FFA antagonizes this action, which may have implications for visfatin bioactivity.

Neurobiological and psychosomatic aspects of infertility in women

2020 ◽  
pp. 21-28
Author(s):  
N. N. Stenyaeva ◽  
D. F. Chritinin
Keyword(s):  
Reproductive Medicine ◽  
Term Treatment ◽  
Social Consequences ◽  
Mental Illnesses ◽  
The Social ◽  
Long Term Treatment ◽  
Psychosomatic Aspects ◽  
Long Term Impact ◽  
The Relationship

In recent years, ideas about the regulation of the autonomic functions of the human body and the psychosomatic effects of sex hormones have expanded significantly. Dysregulation of the HPG-axis is involved in the pathogenesis of a number of stressassociated mental illnesses. Infertility and its long-term treatment is characterized by a long-term impact on patients of various stressful factors. Reproductive medicine has now made impressive advances in biotechnology. Reproductive medicine has now achieved impressive success due to the revolutionary development of biotechnologies. Nevertheless, a significant number of couples have to struggle unsuccessfully with infertility for many years, and the social consequences of this are extremely significant for the family and society as a whole. Taking into account the relationship between the mental and somatic health of infertile women, greater attention of clinicians to the mental sphere of patients, providing forced childless couples with the necessary psychological and psychiatric care will reduce stress during infertility treatment and increase patient satisfaction.

scholarly journals 139 Early Response with Valbenazine and Long-Term Symptom Reduction in Patients with Tardive Dyskinesia: Post Hoc Analysis of the KINECT 3 Study

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 288-289
Author(s):  
Stanley N. Caroff ◽  
Jean-Pierre Lindenmayer ◽  
Stephen R. Marder ◽  
Stewart A. Factor ◽  
Khodayar Farahmand ◽  
...  
Keyword(s):  
Tardive Dyskinesia ◽  
Early Response ◽  
Term Treatment ◽  
Score Change ◽  
Double Blind ◽  
Early Improvement ◽  
Long Term Treatment ◽  
Post Hoc ◽  
Improvement Score

Abstract:Study Objective:Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Valbenazine is a highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of TD in adults. Using data from a long-term study (KINECT 3; NCT02274558), the effects of once-daily valbenazine (40 mg, 80 mg) on TD were assessed using the Abnormal Involuntary Movement Scale (AIMS) in participants who were early responders based on subjective measures, including patient self-report (Patient Global Impression of Change [PGIC]) or clinician judgment (Clinical Impression of Change-Tardive Dyskinesia [CGI-TD]).Methods:Data from KINECT 3 (6-week double-blind, placebo-controlled [DBPC] period; 42-week double-blind extension) were analyzed post hoc. Long-term outcomes included mean change from baseline to Week 48 in AIMS total score (sum of items 1-7) and AIMS response (≥50% total score improvement from baseline) at Week 48. These AIMS outcomes were assessed in participants who achieved early improvement, defined as a PGIC or CGI-TD score of ≤3 (“minimally improved” or better) at Week 2 (first post-baseline visit of the DBPC period). Participants who initially received placebo were not included in the analyses.Results:In participants who received only valbenazine (40 or 80 mg) during KINECT 3 and had available Week 2 assessment, 50% (72/143) had early PGIC improvement (score ≤3) and 43% (61/142) had early CGI-TD improvement (score ≤3). Baseline characteristics were generally similar between participants who achieved early PGIC or CGI-TD improvement and those who did not. Based on available assessments at Week 48, mean AIMS total score change from baseline in participants with early PGIC improvement was similar to those who did not reach the early PGIC improvement threshold (-4.1 [n=35] vs -3.5 [n=41]). Mean AIMS total score change from baseline in participants with early CGI-TD improvement was similar to those who did not achieve early CGI-TD improvement (-4.2 [n=31] vs -3.5 [n=45]). AIMS response at Week 48 was also similar in those who achieved early PGIC and CGI-TD improvement (40% and 42%, respectively) compared to those who did not achieve early PGIC and CGI-TD improvement (39% and 38%, respectively).Conclusions:Results from this long-term valbenazine trial indicate that many participants achieved at least minimal patient- and clinician-reported improvement at Week 2. AIMS outcomes at Week 48 demonstrated long-term reductions in TD severity regardless of early response. More research is needed to understand the association between early improvement and long-term treatment effects, but early non-improvement based on subjective measures may not be predictive of long-term treatment failure.Presented:International Congress of Parkinson’s Disease and Movement Disorders; September 22-26, 2019; Nice, France.Funding Acknowledgements:This study was sponsored by Neurocrine Biosciences, Inc.

scholarly journals Relapse recovery

2019 ◽  
Vol 7 (2) ◽  
pp. e653 ◽  
Author(s):  
Orhun H. Kantarci ◽  
Burcu Zeydan ◽  
Elizabeth J. Atkinson ◽  
Brittani L. Conway ◽  
Carmen Castrillo-Viguera ◽  
...  
Keyword(s):  
Term Treatment ◽  
Benign Disease ◽  
Good Recovery ◽  
Class Iii ◽  
Early Recovery ◽  
Double Blind ◽  
Delayed Treatment ◽  
Long Term Treatment ◽  
Edss Score

ObjectiveTo determine whether basing the decision to initiate immediate vs delayed disease-modifying therapy (DMT) on extent of recovery after initial relapse affects long-term disability accumulation in a multiple sclerosis (MS) evidence-based setting.MethodsWe analyzed the double-blind, placebo-controlled interferon beta-1a 30 mc once a week in clinically isolated syndrome and 10-year-follow-up extension trial. Good recovery after presenting relapse was defined as (1) full early recovery within 28 days of symptom onset (Expanded Disability Status Scale [EDSS] score of 0 at enrollment maintained ≥6 months) and (2) delayed good recovery (EDSS score > 0 at enrollment and improvement from peak deficit to 6th-month or 1-year visit ≥ median). Time from recovery assignment to future disability (EDSS score ≥ 2.5 or ≥4.0) was studied on a relapse-recovery-stratified age axis and immediate vs 3-year delayed treatment initiation with Kaplan-Meier statistics and hazard ratios (HRs).ResultsOne hundred seventy-five/328 patients had good recovery (94 immediate and 81 delayed treatment); 153 did not have good recovery (77 immediate and 76 delayed treatment). HRs for EDSS score ≥2.5 outcome were: delayed treatment without good recovery as reference (HR = 1.0), delayed treatment with good recovery (HR6th-month: 0.67, p = 0.207; HR1st-year: 0.40, p = 0.027), immediate treatment without good recovery (HR6th-month: 0.56, p = 0.061; HR1st-year: 0.40, p = 0.011), and immediate treatment with good recovery (HR6th-month: 0.43, p = 0.014; HR1st-year: 0.48, p = 0.034). Placebo patients were switched to long-term treatment after 3 years, and insufficient EDSS score ≥4.0 outcome events were available to study.ConclusionsIn patients with MS presenting without good recovery after the initial relapse, immediate DMT initiation favorably influences the likelihood of more ambulatory-benign disease akin to patients with good recovery after the initial relapse.Classification of evidenceThis study provides Class III evidence that for patients with MS without good recovery after the initial relapse, immediate DMT initiation increases the likelihood of a benign disease course.

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