scholarly journals Effects of long-term antipsychotics treatment on body weight: A population-based cohort study

2019 ◽  
Vol 34 (1) ◽  
pp. 79-85 ◽  
Author(s):  
Juan Carlos Bazo-Alvarez ◽  
Tim P Morris ◽  
James R Carpenter ◽  
Joseph F Hayes ◽  
Irene Petersen
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Low Dose ◽  
Population Based ◽  
Antipsychotic Treatment ◽  
High Dose ◽  
Olanzapine Treatment ◽  
Short And Long Term ◽  
Higher Doses

Background: Antipsychotics are often prescribed for long-term periods, however, most evidence of their impact on body weight comes from short-term clinical trials. Particularly, impact associated with dosage has been barely studied. Aims: The aim of this study was to describe the short- and long-term change in body weight of people initiated on high or low doses of the three most commonly prescribed second-generation antipsychotics. Methods: Retrospective cohorts of individuals with a diagnosed psychotic disorder observed from 2005 to 2015 in the UK primary care. The exposure was the first prescription of olanzapine, quetiapine or risperidone. The main outcome was change in body weight four years before and four years after initiation of antipsychotic treatment, stratified on sex and ‘low’ or ‘high’ dose. Results: In total, 22,306 women and 16,559 men were observed. Olanzapine treatment was associated with the highest change in weight, with higher doses resulting in more weight gain. After 4 years, given a high dose of olanzapine (> 5 mg), women gained on average +6.1 kg; whereas given a low dose (⩽ 5 mg), they gained +4.4 kg. During the first six weeks of olanzapine treatment, they gained on average +3.2 kg on high dose and +1.9 kg on low dose. The trends were similar for men. Individuals prescribed risperidone and quetiapine experienced less weight gain in both the short- and long-term. Conclusions: Olanzapine treatment was associated with the highest increase in weight. Higher doses were associated with more weight gain. Doctors should prescribe the lowest effective dose to balance mental-health benefits, weight gain and other adverse effects.

scholarly journals The Effect of Long-Term Low-Dose Atropine on Refractive Progression in Myopic Australian School Children

2021 ◽  
Vol 10 (7) ◽  
pp. 1444
Author(s):  
William Myles ◽  
Catherine Dunlop ◽  
Sally A. McFadden
Keyword(s):  
Low Dose ◽  
High Dose ◽  
Eye Drops ◽  
Myopia Progression ◽  
At Risk Children ◽  
Slow Group ◽  
Blue Eyes ◽  
Global Population ◽  
Axial Growth

Myopia will affect half the global population by 2050 and is a leading cause of vision impairment. High-dose atropine slows myopia progression but with undesirable side-effects. Low-dose atropine is an alternative. We report the effects of 0.01% or 0.005% atropine eye drops on myopia progression in 13 Australian children aged between 2 and 18 years and observed for 2 years without and up to 5 years (mean 2.8 years) with treatment. Prior to treatment, myopia progression was either ‘slow’ (more positive than −0.5D/year; mean −0.19D/year) or ‘fast’ (more negative than −0.5D/year; mean −1.01D/year). Atropine reduced myopic progression rates (slow: −0.07D/year, fast: −0.25D/year, combined: before: −0.74, during: −0.18D/year, p = 0.03). Rebound occurred in 3/4 eyes that ceased atropine. Atropine halved axial growth in the ‘Slow’ group relative to an age-matched model of untreated myopes (0.098 vs. 0.196mm/year, p < 0.001) but was double that in emmetropes (0.051mm/year, p < 0.01). Atropine did not slow axial growth in ‘fast’ progressors compared to the age-matched untreated myope model (0.265 vs. 0.245mm/year, p = 0.754, Power = 0.8). Adverse effects (69% of patients) included dilated pupils (6/13) more common in children with blue eyes (5/7, p = 0.04). Low-dose atropine could not remove initial myopia offsets suggesting treatment should commence in at-risk children as young as possible.

scholarly journals Treatment-resistant schizophrenia characterised by dopamine supersensitivity psychosis and efficacy of asenapine

2021 ◽  
Vol 14 (4) ◽  
pp. e242495
Author(s):  
Nagara Takao ◽  
Toshiya Murai ◽  
Hironobu Fujiwara
Keyword(s):  
Animal Studies ◽  
Significant Proportion ◽  
Antipsychotic Treatment ◽  
High Dose ◽  
Receptor Density ◽  
Treatment Resistant ◽  
Psychomotor Activity ◽  
Receptor Blockers ◽  
Dopamine Supersensitivity

Dopamine supersensitivity psychosis (DSP) frequently arises with long-term antipsychotic treatment and accounts for a significant proportion of treatment-resistant schizophrenia. The mechanism underlying DSP is thought to be a compensatory increase in dopamine receptor density in the striatum caused by long-term antipsychotic treatment. Previous animal studies have reported that antipsychotics increase serotonin 5-HT2A receptor density in the striatum and that 5-HT2A receptor blockers suppress dopamine-sensitive psychomotor activity, which may be linked to the pathophysiology of DSP. In this paper, we describe a patient who was hospitalised with treatment-resistant schizophrenia. Following treatment with high-dose antipsychotic polypharmacy for 10 weeks, the patient experienced worsening of psychotic and extrapyramidal symptoms. The patient was then started on second-generation antipsychotic asenapine while other antipsychotics were tapered off, resulting in improvement of these symptoms. Retrospectively, we presumed that the high-dose antipsychotic polypharmacy caused DSP, which was effectively treated by the potent 5-HT2A receptor antagonism of asenapine.

Impact of short- and long-term exposure to air pollution on blood pressure: A two-decade population-based study in Tehran

2021 ◽  
Vol 234 ◽  
pp. 113719
Author(s):  
Alireza Khajavi ◽  
Seyed Saeed Tamehri Zadeh ◽  
Fereidoun Azizi ◽  
Robert D. Brook ◽  
Hengameh Abdi ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Air Pollution ◽  
Population Based ◽  
Population Based Study ◽  
Short And Long Term

Renoprotective effects of a novel Nox1/4 inhibitor in a mouse model of Type 2 diabetes

2012 ◽  
Vol 124 (3) ◽  
pp. 191-202 ◽  
Author(s):  
Mona Sedeek ◽  
Alex Gutsol ◽  
Augusto C. Montezano ◽  
Dylan Burger ◽  
Aurelie Nguyen Dinh Cat ◽  
...  
Keyword(s):  
Body Weight ◽  
Low Dose ◽  
Transforming Growth Factor ◽  
Disease Process ◽  
Thiobarbituric Acid ◽  
Transforming Growth Factor Β ◽  
Mitogen Activated Protein Kinase ◽  
High Dose ◽  
Diabetic Mice ◽  
Mitogen Activated Protein

Nox (NADPH oxidase)-derived ROS (reactive oxygen species) have been implicated in the development of diabetic nephropathy. Of the Nox isoforms in the kidney, Nox4 is important because of its renal abundance. In the present study, we tested the hypothesis that GKT136901, a Nox1/4 inhibitor, prevents the development of nephropathy in db/db (diabetic) mice. Six groups of male mice (8-week-old) were studied: (i) untreated control db/m, (ii) low-dose GKT136901-treated db/m (30 mg/kg of body weight per day), (iii) high-dose GKT136901-treated db/m (90 mg/kg of body weight per day), (iv) untreated db/db; (v) low dose GKT136901-treated db/db; and (vi) high-dose GKT136901-treated db/db. GKT136901, in chow, was administered for 16 weeks. db/db mice developed diabetes and nephropathy as evidenced by hyperglycaemia, albuminuria and renal injury (mesangial expansion, tubular dystrophy and glomerulosclerosis). GKT136901 treatment had no effect on plasma glucose or BP (blood pressure) in any of the groups. Plasma and urine TBARSs (thiobarbituric acid-reacting substances) levels, markers of systemic and renal oxidative stress, respectively, were increased in diabetic mice. Renal mRNA expression of Nox4, but not of Nox2, increased, Nox1 was barely detectable in db/db. Expression of the antioxidant enzyme SOD-1 (superoxide dismutase 1) decreased in db/db mice. Renal content of fibronectin, pro-collagen, TGFβ (transforming growth factor β) and VCAM-1 (vascular cell adhesion molecule 1) and phosphorylation of ERK1/2 (extracellular-signal-regulated kinase 1/2) were augmented in db/db kidneys, with no change in p38 MAPK (mitogen-activated protein kinase) and JNK (c-Jun N-terminal kinase). Treatment reduced albuminuria, TBARS and renal ERK1/2 phosphorylation and preserved renal structure in diabetic mice. Our findings suggest a renoprotective effect of the Nox1/4 inhibitor, possibly through reduced oxidative damage and decreased ERK1/2 activation. These phenomena occur independently of improved glucose control, suggesting GKT136901-sensitive targets are involved in complications of diabetes rather than in the disease process.

Enlargement of cerebrospinal fluid spaces in long-term benzodiazepine abusers

1987 ◽  
Vol 17 (4) ◽  
pp. 869-873 ◽  
Author(s):  
C. Schmauss ◽  
J.-C. Krieg
Keyword(s):  
Low Dose ◽  
Matched Control ◽  
Control Group ◽  
High Dose ◽  
Withdrawal Therapy ◽  
The Mean ◽  
Dose Dependent ◽  
Dose Dependent Effect ◽  
Age And Sex

SynopsisIn 17 benzodiazepine (BDZ) dependent in-patients a CT scan was performed before initiation of withdrawal therapy. The evaluation of the ventricular to brain ratio (VBR) by standardized and computerized measurements revealed significantly higher mean VBRs for both high-and low-dose BDZ-dependent patients compared to the mean VBR of an age- and sex-matched control group. In addition, the mean VBR of high-dose BDZ-dependent patients (N = 8) was significantly higher than the mean VBR of low-dose BDZ-dependent patients (N = 9). This difference could not be accounted for by the age of the patients or duration of BDZ-dependency and, therefore, suggests a dose-dependent effect of BDZs on the enlargement of internal CSF-spaces. On the other hand, higher values for the width of external CSF-spaces were found to be related to increasing age of the patients and duration of BDZ-dependency.

Short and long-term outcome of treatment with high-dose melphalan and stem cell transplantation for multiple myeloma-associated AL amyloidosis

2009 ◽  
Vol 89 (6) ◽  
pp. 579-584 ◽  
Author(s):  
Saulius Girnius ◽  
David C. Seldin ◽  
Martha Skinner ◽  
Kathleen T. Finn ◽  
Karen Quillen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
High Dose ◽  
Al Amyloidosis ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Short And Long Term ◽  
High Dose Melphalan

Exacerbated febrile responses to LPS, but not turpentine, in TNF double receptor-knockout mice

1997 ◽  
Vol 272 (2) ◽  
pp. R563-R569 ◽  
Author(s):  
L. R. Leon ◽  
W. Kozak ◽  
J. Peschon ◽  
M. J. Kluger
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Motor Activity ◽  
Knockout Mice ◽  
Low Dose ◽  
Late Phase ◽  
High Dose ◽  
Wild Type ◽  
Inflammatory Stimuli ◽  
Necrosis Factor

We examined the effects of injections of systemic [lipopolysaccharide (LPS), 2.5 mg/kg or 50 pg/kg ip] or local (turpentine, 100 microl sc) inflammatory stimuli on fever, motor activity, body weight, and food intake in tumor necrosis factor (TNF) double receptor (TNFR)-knockout mice. A high dose of LPS resulted in exacerbated fevers in TNFR-knockout mice compared with wild-type mice for the early phase of fever (3-15 h); the late phase of fever (16-24 h) and fevers to a low dose of LPS were similar in both groups. Motor activity, body weight, and food intake were similarly reduced in both groups of mice after LPS administration. In response to turpentine, TNFR-knockout and wild-type mice developed virtually identical responses to all variables monitored. These results suggest that 1) TNF modulates fevers to LPS dose dependently, 2) TNF does not modulate fevers to a subcutaneous injection of turpentine, and 3) knockout mice may develop cytokine redundancy in the regulation of the acute phase response to intraperitoneally injected LPS or subcutaneously injected turpentine.

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