Lurasidone and risk for metabolic syndrome: results from short- and long-term clinical studies in patients with schizophrenia

CNS Spectrums ◽  
2020 ◽  
pp. 1-11
Author(s):  
Michael Tocco ◽  
John W. Newcomer ◽  
Yongcai Mao ◽  
Andrei Pikalov ◽  
Antony Loebel
Keyword(s):  
Metabolic Syndrome ◽  
Dose Range ◽  
Dose Effect ◽  
Short Term ◽  
Open Label ◽  
Quetiapine Xr ◽  
Long Term Treatment ◽  
Short And Long Term ◽  
Term Data

Abstract Objective To assess the effects of treatment with lurasidone on risk for metabolic syndrome (MetS) in patients with schizophrenia. Methods Rates of metabolic syndrome during treatment with lurasidone (40-160 mg/d) were analyzed using pooled, short-term data from three randomized, double-blind, placebo-controlled studies (vs olanzapine and quetiapine XR); long-term data from two active-comparator-controlled studies (vs risperidone and quetiapine XR); and data from two open-label studies in which patients were switched from olanzapine or risperidone to lurasidone. Results MetS was defined based on the National Cholesterol Education Program criteria. In short-term studies, the odds of meeting criteria for MetS at week 6 LOCF (adjusted for baseline metabolic syndrome status) was similar for the lurasidone and placebo groups (OR = 1.18; [95% CI, 0.81-1.71]; P = .39), but the odds (vs placebo) were significantly greater for olanzapine (OR = 2.81; [95% CI, 1.53-5.15]; P < .001) and quetiapine (OR = 3.49; [95% CI, 1.93-6.29]; P < .0001). No dose effect was observed for lurasidone across the dose range of 40-160 mg/d. In long-term studies, the odds of MetS after 12 months of treatment was significantly higher for risperidone compared with lurasidone (OR = 2.12; 95% CI, 1.15-3.90; P = .016) and for quetiapine XR compared with lurasidone (OR = 3.92; 95% CI, 1.15-13.40; P = .029). In open-label extension studies, the rate of MetS decreased in patients switched to lurasidone after 6 weeks of treatment with olanzapine or 12 months of treatment with risperidone. Conclusion In this analysis of lurasidone clinical trials, the odds of developing metabolic syndrome were minimal during short- and long-term treatment with lurasidone (40-160 mg/d).

Fluvoxamine in the Treatment of Trichotillomania: An 8-Week, Open-Label Study

CNS Spectrums ◽  
1998 ◽  
Vol 3 (9) ◽  
pp. 64-71 ◽  
Author(s):  
Gary A. Christenson ◽  
Scott J. Crow ◽  
James E. Mitchell ◽  
Thomas B. Mackenzie ◽  
Ross D. Crosby ◽  
...  
Keyword(s):  
Treatment Response ◽  
Term Treatment ◽  
Hair Pulling ◽  
Short Term ◽  
Open Label ◽  
Short Term Treatment ◽  
Open Label Study ◽  
Label Study ◽  
Long Term Treatment

AbstractThis short-term, open-label study investigates short- and long-term effects of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine for the treatment of trichotillomania (TTM). Additionally, this study aimed to test the hypothesis that the presence of hair pulling compulsiveness is predictive of SSRI response. Nineteen subjects meeting the Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised, (DSM-III-R) criteria for TTM were treated with fluvoxamine at doses up to 300 mg/day. Random regression analysis of change across time for patients who completed the study (n=14) and those who dropped out (n=5) revealed statistically significant improvements in Physician Rating Scale, hair-pulling episodes, Trichotillomania Impairment Scale, and Trichotillomania Symptom Severity Scale, but not in estimated amount of hair pulled. In addition, the percentage of patients' focused or compulsive hair-pulling symptoms was predictive of treatment response. Unfortunately, all three subjects who entered long-term treatment displayed substantial movement back toward baseline by the end of 6 months. We concluded that fluvoxamine produces moderate reductions in symptoms during the short-term treatment of TTM and that the presence of focused or compulsive hair pulling may be predictive of treatment response. However, responses may be short lived when treatment is extended.

scholarly journals Mitochondrial and Oxidative Impacts of Short and Long-term Administration of HAART on HIV Patients

2020 ◽  
Vol 15 (2) ◽  
pp. 110-124
Author(s):  
Joy E. Ikekpeazu ◽  
Oliver C. Orji ◽  
Ikenna K. Uchendu ◽  
Lawrence U.S. Ezeanyika
Keyword(s):  
Treatment Group ◽  
Term Treatment ◽  
Short Term ◽  
Short Term Treatment ◽  
Hiv Patients ◽  
Long Term Treatment ◽  
Term Administration ◽  
Short And Long Term ◽  
One Year

Background and Objective: There may be a possible link between the use of HAART and oxidative stress-related mitochondrial dysfunction in HIV patients. We evaluated the mitochondrial and oxidative impacts of short and long-term administration of HAART on HIV patients attending the Enugu State University Teaching (ESUT) Hospital, Enugu, Nigeria following short and long-term therapy. Methods: 96 patients categorized into four groups of 24 individuals were recruited for the study. Group 1 comprised of age-matched, apparently healthy, sero-negative individuals (the No HIV group); group 2 consisted of HIV sero-positive individuals who had not started any form of treatment (the Treatment naïve group). Individuals in group 3 were known HIV patients on HAART for less than one year (Short-term treatment group), while group 4 comprised of HIV patients on HAART for more than one year (Long-term treatment group). All patients were aged between 18 to 60 years and attended the HIV clinic at the time of the study. Determination of total antioxidant status (TAS in nmol/l), malondialdehyde (MDA in mmol/l), CD4+ count in cells/μl, and genomic studies were all done using standard operative procedures. Results: We found that the long-term treatment group had significantly raised the levels of MDA, as well as significantly diminished TAS compared to the Short-term treatment and No HIV groups (P<0.05). In addition, there was significantly elevated variation in the copy number of mitochondrial genes (mtDNA: D-loop, ATPase 8, TRNALEU uur) in the long-term treatment group. Interpretation and Conclusion: Long-term treatment with HAART increases oxidative stress and causes mitochondrial alterations in HIV patients.

scholarly journals Protein Metabolism in Acromegaly: Differential Effects of Short- and Long-Term Treatment

2007 ◽  
Vol 92 (4) ◽  
pp. 1479-1484 ◽  
Author(s):  
James Gibney ◽  
Troels Wolthers ◽  
Morton G. Burt ◽  
Kin-Chuen Leung ◽  
A. Margot Umpleby ◽  
...  
Keyword(s):  
Protein Oxidation ◽  
Protein Metabolism ◽  
Normal Subjects ◽  
Term Treatment ◽  
Protein Breakdown ◽  
Short Term ◽  
Leucine Oxidation ◽  
Long Term Treatment ◽  
Short And Long Term

Abstract Context: GH acutely increases body protein by stimulating protein synthesis and reducing protein oxidation. Objective: The objective of the study was to determine whether these changes in protein metabolism are sustained in long-term GH excess and reversed by correction. Design: We conducted a cross-sectional study in 16 acromegalic and 18 normal subjects and a longitudinal study in which acromegalic subjects were studied before and after short-term (n = 8) or long-term (n = 10) treatment. Setting: The study was conducted at a clinical research center. Main Outcome Measures: Whole-body rates of leucine appearance (leucine Ra; an index of protein breakdown), leucine oxidation, and nonoxidative leucine disposal (NOLD; an index of protein synthesis) estimated using infusion of 1-[13C] leucine were measured. Results: Leucine Ra and NOLD were greater (P &lt; 0.01) in acromegalic compared with normal subjects, whereas leucine oxidation did not differ. Leucine oxidation increased significantly (P &lt; 0.05) after short-term treatment but returned to baseline after long-term treatment. Both leucine Ra and NOLD decreased significantly (P &lt; 0.05) after short- and long-term treatment. Adjustment for body composition did not affect results. Conclusions: In acromegalic subjects, protein breakdown and synthesis are increased, whereas protein oxidation does not differ from normal subjects. Protein oxidation increases transiently, whereas protein breakdown and synthesis are stably reduced after treatment. Because protein oxidation represents irreversible loss, we conclude that the normal state of protein oxidation found in acromegaly and after long-term treatment represents metabolic adaptation, which maintains protein mass at a steady state after stable changes in GH status.

scholarly journals 160 Lurasidone and Metabolic Syndrome: Results from Short- and Long-Term Clinical Studies in Patients with Bipolar Depression

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 302-303
Author(s):  
Michael Tocco ◽  
John W. Newcomer ◽  
Yongcai Mao ◽  
Andrei Pikalov
Keyword(s):  
Metabolic Syndrome ◽  
Adjunctive Therapy ◽  
Bipolar Depression ◽  
Prevention Study ◽  
Short Term ◽  
Post Hoc Analysis ◽  
Short And Long Term ◽  
Post Hoc ◽  
Therapy Studies

Abstract:Background:Among patients with depressive disorders, the prevalence of metabolic syndrome (MetS) is estimated to range from 35-40% and has been associated with increased mortality rates. The aim of this post-hoc analysis was to assess the effect of treatment with lurasidone on the prevalence of MetS in patients with bipolar depression.Method:Lurasidone data (dose range, 20-120 mg/d) used in the current analyses consisted of 3 double-blind (DB), placebo-controlled, 6-week studies in adults with bipolar I depression (total N=1,192), consisting of 1 monotherapy, and 2 adjunctive therapy trials with lithium or valproate. Patients who completed the short-term trials continued into a 6-month open-label (OL) extension study, with 6-month (LOCF-endpoint) data available on 274 patients treated with lurasidone monotherapy, and 436 patients treated with lurasidone adjunctive therapy. Also analyzed was a recurrence prevention study in stabilized bipolar patients who completed up to 20 weeks of OL adjunctive treatment with lurasidone, and then were randomized to 28 weeks of DB adjunctive therapy with lurasidone or placebo (N=497). MetS was defined based on NCEP ATP III criteria (2005 revision).Results:In the short-term monotherapy and adjunctive therapy studies, the proportion of patients at baseline meeting NCEP III criteria for MetS were 27.6% and 23.6%, respectively, for lurasidone, and 23.8% and 25.1%, respectively, for placebo; and at week 6 (LOCF) the proportion with MetS was 27.5% and 26.6%, respectively, for lurasidone and 29.9% and 20.2%, respectively, for placebo. The proportion of patients who did not meet MetS criteria at baseline but developed MetS at week 6 (LOCF) was similar for lurasidone vs. placebo in the monotherapy study (9.9% vs. 11.6%); and in the two adjunctive therapy studies (10.3% vs. 8.3%). During the 6-month OL extension study, the proportion of patients treated with lurasidone monotherapy and adjunctive therapy who did not meet MetS criteria at OL baseline but developed MetS at month 6 (LOCF) was 11.7% and 11.9%, respectively. Conversely, the proportion of patients who met MetS criteria at OL baseline, but no longer met criteria at month 6 (LOCF) was 9.5% and 7.7%, respectively. In the 20-week, OL phase of the recurrence prevention study, the proportion of patients treated with adjunctive lurasidone who did not meet MetS criteria at OL baseline but developed MetS at endpoint was 11.5% (LOCF). After up to 28 weeks of DB treatment, the proportion of patients who did not meet MetS criteria at DB baseline but developed MetS at endpoint was 9.0% in the adjunctive lurasidone group, and 10.5% in the adjunctive placebo group (LOCF).Conclusion:This post-hoc analysis found that short- and long-term treatment with lurasidone was associated with a relatively low risk for the development of metabolic syndrome in patients with bipolar I disorder. These findings are consistent with similar analyses in patients with schizophrenia.Funding Acknowledgements:Supported by funding from Sunovion Pharmaceuticals Inc.

scholarly journals Adalimumab for long-term treatment of psoriatic arthritis: 2-year data from the Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT)

2008 ◽  
Vol 68 (5) ◽  
pp. 702-709 ◽  
Author(s):  
P J Mease ◽  
P Ory ◽  
J T Sharp ◽  
C T Ritchlin ◽  
F Van den Bosch ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Term Treatment ◽  
Joint Disease ◽  
Short Term ◽  
Open Label ◽  
Short Term Treatment ◽  
Double Blind ◽  
Long Term Treatment ◽  
Adalimumab Treatment

Objective:To evaluate the long-term effectiveness and tolerability of adalimumab in the treatment of psoriatic arthritis (PsA).Methods:Patients with PsA who completed a 24-week, double-blind study of adalimumab versus placebo were eligible to enroll in an open-label extension study and receive adalimumab 40 mg subcutaneously every other week for up to an additional 120 weeks. At the time of this analysis, available efficacy evaluations throughout 2 years of treatment (n  =  245) included American College of Rheumatology (ACR) 20%, 50% and 70% improvement scores, measures of joint disease and skin disease, disability and quality of life; modified total Sharp scores (mTSS) were available for 2.75 years of treatment for patients who received adalimumab in the 24-week study.Results:After 24 weeks of double-blind treatment, the mean change in mTSS was −0.2 for the adalimumab group (N  =  144) and 1.0 for the placebo group (N  =  152; p<0.001), and outcomes for all individual ACR component variables were significantly improved in adalimumab compared with placebo-treated patients. Compared with 24-week responses, inhibition of radiographic progression and improvements in joint disease were maintained in most patients during long-term, open-label adalimumab treatment. Also, improvements in skin disease were maintained, with >20% of patients achieving the strict criterion of psoriasis area and severity index 100. The nature and frequency of adverse events during long-term adalimumab treatment were consistent with the safety profile during short-term treatment.Conclusions:The clinical and radiographic efficacy of adalimumab demonstrated during short-term treatment was sustained during long-term treatment. Adalimumab has a favourable risk–benefit profile in patients with PsA.Trial registration number:NCT00195689.

scholarly journals Long-term Outcomes and Quality of Life Following Parotidectomy for Benign Disease: A Cohort Study

2020 ◽  
Author(s):  
Michaela Plath ◽  
Matthias Sand Sand ◽  
Peter K. Plinkert ◽  
Ingo Baumann ◽  
Karim Zaoui
Keyword(s):  
Quality Of Life ◽  
Long Term Outcomes ◽  
Short Term ◽  
Minor Problem ◽  
Long Term Follow Up ◽  
Short And Long Term ◽  
Term Data

Abstract Backround:Parotidectomy may be burdened by numerous complications that may worsen subjects' quality of life (QoL). So far, the literature still lacks of long-term data (> 10 years) answering to the question what impacted the patients the most on QOL after parotidectomy compared to well-published short-term data.Methods:A prospective long-term follow-up study was carried out. Participants were divided into three groups concerning the follow-up: short-term (ST; 6 postoperative weeks), long-term (LT; 13 years postoperative) and short- and long-term (SLT) on same patient collective. QOL was assessed by the Parotidectomy Outcome Inventory (POI-8). Demographic and clinical data were collected from all patients. Operative reports were used to classify all parotidectomies as great nerve auricular (GAN) “preserving” or GAN “sacrificing” surgical preparations.Results:74 LT, 57 ST and 33 SLT patients were enrolled in this study. Hypoesthesia posed the major short- and long-term problem whereas facial palsy posed the minor problem. Pain (p < 0.01) and hypoesthesia (p < 0.001) significantly improved from six weeks to 13 years after parotidectomy as well as the overall POI-8 score (p = 0.04). The disease-specific impairment rate decreased from short (≈ 70%) to long-term (≈ 30%) follow-up. Sacrifice of the auricular nerve was associated with hypoesthesia in the ST-cohort (p = 0.028).Conclusion:To our knowledge, this study represents the longest follow-up of patients undergoing parotidectomy. Hypoesthesia significantly improved but still remains on long-follow-up without impacting QOL. As part of the preoperative informed consent, prolonged or permanent hypoesthesia should be explicitly emphasized.Trial registration:This study was prospectively approved and registered by the local Ethics Committee (Project Trial No: S-300/2007 and S-443/2018).

scholarly journals Effects of short- and long-term feeding of L-carnitine and congeners on the production of eicosanoids from rat peritoneal leucocytes

1994 ◽  
Vol 72 (5) ◽  
pp. 785-793 ◽  
Author(s):  
Ingrid M. Garrelds ◽  
Graham R. Elliott ◽  
Freek J. Zijlstra ◽  
Iván L. Bonta
Keyword(s):  
Term Treatment ◽  
Short Term ◽  
Young Rats ◽  
Long Term Treatment ◽  
Prostaglandin F ◽  
Old Rats ◽  
Short And Long Term ◽  
Propionyl Carnitine ◽  
In Cells

The effect of short- and long-term feeding with L-carnitine, L-acetyl carnitine and L-propionyl carnitine on the production of eicosanoids front in vitro stimulated carrageenan-induced rat peritoneal macrophages was investigated. Both young (4 weeks) and old (18 months) rats were used. A lower number of cells was isolated from the peritonea of treated than control young rats after 4 d feeding, but after 60 d no differences were observed. A similar reduction in cell number was found when old animals were given L-acetyl carnitine or L-propionyl carnitine (acutely) or L-acetyl carnitine or L-carnitine (chronically). Plasma carnitine levels were higher in young rats given carnitine both chronically and acutely. Carnitine derivatives were without effect. In contrast, levels of total carnitine in the plasma of old rats given L-carnitine and L-acetyl carnitine for 4 d and 60 d were higher than in controls. There was no correlation between total plasma carnitine level and effects on prostaglandin, thromboxane and leukotriene B4 (LTB4) production. In young rats the most important changes were observed in relation to the production of prostacyclin (PGI2), measured as 6 keto-prostaglandin Flα. Prostacyclin production was higher in the groups given carnitine or its derivatives. The net result of the changes in PGI2 was that the 6 keto-prostaglandin F1α: thromboxane B2 and the 6 keto-prostaglandin Flα:LTB4 ratios tended to be higher in cells from young animals following short-term feeding with L-carnitine. When young rats were given carnitine compounds for 60 d PGI2 production was lower in cells from L-acetyl carnitine- and L-propionyl carnitine-fed animals. The net result of the changes in PGI2 was that the 6 keto-prostaglandin F1α: thromboxane B2 and the 6 keto-prostaglandin F1α:LTB4 ratios were lower in cells from animals fed with carnitine compounds. In old rats the PGI2 production was lower after short-term feeding with carnitine compounds and was higher after long-term feeding. LTB4 production was lower after L-carnitine and L-acetyl carnitine treatment for 4 d and also lower after 60 d treatment with L-acetyl carnitine. The net results of the changes in PGI2 were that the 6 keto-prostaglandin F1α: thromboxane B2 and the 6 keto-prostaglandin F1α:LTB4 ratios were lower after short-term feeding of all three compounds and higher after the long-term treatment with L-acetyl carnitine and L-propionyl carnitine in old rats. By long-term treatment with low-dose aspirin of patients with heart failure and claudication, the 6 keto-prostaglandin F1α: thromboxane B2 ratio is positively increased, which is a beneficial cardioprotective effect. The mechanism of action of carnitine in heart failure and claudication could also be achieved by an increase of this ratio. Our results suggest that elderly patients could be treated chronically by carnitine to obtain this beneficial effect.

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