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Biomedical subjects

Gary Remington

Publications and source records attributed to Gary Remington.

At least 19 recordsLinked to original sources
PubMed2026

Pharmacological Interventions for Weight Reduction in Patients With Schizophrenia Treated With Antipsychotics: A Systematic Review and Network Meta-Analysis.

IMPORTANCE: Significant weight gain is a concerning adverse effect of antipsychotic medications experienced by patients with schizophrenia spectrum disorders (SSDs). Its high prevalence and significant contribution to cardiometabolic morbidity in this population warrant better consensus on the management of antipsychotic-induced weight gain and related comorbidity. OBJECTIVES: To evaluate the association between pharmacological interventions and changes in body weight among antipsychotic-treated patients with SSDs. DATA SOURCES: Ovid MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP) Search Portal were searched up to December 5, 2025. STUDY SELECTION: Randomized clinical trials examining any pharmacological intervention for weight reduction in antipsychotic-treated patients with SSDs were included. No restrictions to study duration were applied. DATA EXTRACTION AND SYNTHESIS: A systematic review and frequentist random-effects network meta-analysis was conducted. Certainty in the evidence was assessed using the Confidence in Network Meta-Analysis (CINeMA) tool. The first round of data analysis took place between May 2025 to November 2025 and was updated in December 2025. MAIN OUTCOMES AND MEASURES: The primary outcome was change in body weight following treatment with pharmacological agent vs placebo or standard care. Secondary outcomes included other anthropometric and metabolic parameters. RESULTS: A total of 95 studies examining 39 individual pharmacological interventions were included in this review (pooled N = 5898). The network meta-analysis found that semaglutide (mean difference [MD], -10.98 kg; 95% CI, -13.33 to -8.62; k = 3; moderate certainty), liraglutide (MD, -5.43 kg; 95% CI, -8.54 to -2.33; k = 2; moderate certainty), topiramate (MD, -3.95 kg; 95% CI, -5.89 to -2.02; k = 5; moderate certainty), metformin (MD, -3.86 kg; 95% CI, -5.02 to -2.70; k = 16; moderate certainty), and exenatide (MD, -2.97 kg; 95% CI, -5.83 to -0.11; k = 3; moderate certainty) were associated with the most significant reductions in body weight compared to placebo. Other interventions including ramelteon, nizatidine, and aripiprazole were also found to be associated with weight-reducing effects but with very low certainty of evidence. Clinically meaningful weight change of 5% or greater was observed with semaglutide and metformin. Beneficial effects on other metabolic outcomes were also noted with several of the medications, and there were no major concerns with gastrointestinal adverse effects or leaving the study early (ie, dropouts) between interventions. CONCLUSIONS AND RELEVANCE: This systematic review and network meta-analysis found substantial variability in weight-related outcomes across pharmacological interventions for antipsychotic-treated individuals with SSDs. Semaglutide, liraglutide, topiramate, metformin, and exenatide were associated with the greatest reductions in body weight and were supported by the highest-certainty evidence, providing guidance for clinicians managing antipsychotic-associated weight gain.

Humans↗
PubMed2007

The use of electronic monitoring (MEMS) to evaluate antipsychotic compliance in outpatients with schizophrenia.

Compliance with antipsychotic treatment is a well-recognized concern in the ongoing management of individuals with schizophrenia. The present investigation incorporated the Medication Event Monitoring System (MEMS) to evaluate compliance in a group of outpatients (N=52) with schizophrenia or schizoaffective disorder. Evaluating compliance as a dichotomous variable and using a threshold of 80%, the rate of noncompliance as measured by MEMS was 52%, considerably higher than self-report (3%), clinician rating (24%) and pill count (25%). The ability of treating clinicians to predict compliance/noncompliance was limited: 13 of 31 (42%) subjects they rated as compliant were noncompliant while 4 of 9 (44%) rated as noncompliant were actually compliant according to MEMS. Factors most consistently associated with noncompliance were higher total symptom scores and dosing complexity i.e., greater than once daily. Based on MEMS data, the overall mean level of compliance was 66%; however, it remains unclear as to what threshold is associated with a compromise in clinical response. More sophisticated measurement tools such as MEMS may assist us in better understanding how level and pattern of antipsychotic noncompliance, factors that at present remain poorly understood, impact on symptom exacerbation.

Adult↗
PubMed2006

Body mass index, waist circumference and quality of life in individuals with schizophrenia.

OBJECTIVE: The primary objective was to examine the differential relationship between waist circumference, body mass index, and self-reported quality of life in patients with schizophrenia. METHOD: Individuals with DSM-IV schizophrenia (n=90) were interviewed to obtain sociodemographic data, complete a Quality of Life questionnaire (the MOS SF-12) and have measurements taken of height, weight (kg), and waist circumference (cm). Multiple regression analysis was used to assess the associations between adiposity measures (BMI, WC) and quality of life outcomes (PCS, MCS). RESULTS: Mental component score (MCS) was not significantly related to either of the weight related measures. After adjustment for gender and age, both BMI alone and WC alone were significant predictors of PCS. When both BMI and WC were included in the same regression model, only WC remained a significant predictor of PCS. CONCLUSIONS: Quality of life in schizophrenic patients is related to measures of body weight. The relationship is strongest using waist circumference as the primary measure. This provides further support for routinely incorporating this measure within research and clinical assessments.

Adult↗
PubMed2006

Association study of tardive dyskinesia and twelve DRD2 polymorphisms in schizophrenia patients.

Tardive dyskinesia (TD) is a side-effect of chronic antipsychotic medication. Abnormalities in dopaminergic activity in the nigrostriatal system have been most often suggested to be involved because the agents which cause TD share in common potent antagonism of dopamine D2 receptors (DRD2), that notably is not balanced by effects such as more potent serotonin (5-HT)2A antagonism. Thus, a number of studies have focused on the association of dopamine system gene polymorphisms and TD. The most consistent findings have been found with the Ser9Gly polymorphism of the DRD3 gene. Although DRD2 has long been hypothesized to be the main target for antipsychotics, only a few polymorphisms in DRD2 have been investigated for their potential involvement in the aetiology of TD. In the present study, we investigated 12 polymorphisms spanning the DRD2 gene and their association with TD in our European Caucasian (n=202) and African-American (n=30) samples. Genotype frequencies for a functional polymorphism, C957T (Duan et al., 2003; Hirvonen et al., 2004), and the adjacent C939T polymorphism were found to be significantly associated with TD (p=0.013 and p=0.022 respectively). DRD2 genotypes were not significantly associated with TD severity as measured by AIMS (Abnormal Involuntary Movement Scale) with the exception of a trend for C939T (p=0.071). Both TD and total AIMS scores were found to be significantly associated with two-marker haplotypes containing C939T and C957T (p=0.021 and p=0.0087 respectively). Preliminary results indicated that C957T was also associated with TD in our African-American sample (p=0.047). Taken together, the present study suggests that DRD2 may be involved in TD in the Caucasian population, although further studies are warranted.

Adult↗
PubMed2006

Impact of haloperidol, a dopamine D2 antagonist, on cognition and mood.

Blocking dopamine (DA) D(2) receptors is the sine qua non of antipsychotic activity. However, it is this same process that accounts for their liability to produce extrapyramidal symptoms (EPS) and hyperprolactinemia. It remains unclear, though, whether there are other negative consequences that might result from DA D(2) blockade. For example, previous research has demonstrated a robust relationship between DA and both cognition and mood. The present study was designed to evaluate the impact of DA D(2) antagonism on each of these domains. Healthy participants (N = 59) were randomized to receive a single oral dose of 1, 3 or 5 mg of haloperidol or placebo. Participants were tested on cognitive and mood measures at baseline, 4 and 24 h post-administration of medication. In terms of cognition, the greatest negative impact was on sustained attention, reaction time and speed of information processing, with the effect on sustained attention reaching statistical significance. For mood, the greatest negative impact occurred on measures of contentment, anger and confusion, with the effect on contentment reaching statistical significance. Global effects for both cognition and mood domains were greatest at 4 h post-administration of haloperidol and dose-dependent. The present results suggest that DA D(2) blockade, as induced by haloperidol, produces important deficits that extend beyond motor or endocrine changes.

Adolescent↗
PubMed2006

A PET study evaluating dopamine D2 receptor occupancy for long-acting injectable risperidone.

OBJECTIVE: Long-acting injectable risperidone represents the first clinically available depot atypical antipsychotic. The present study used positron emission tomography (PET) to evaluate its dopamine D(2) binding profile at doses of 25, 50, or 75 mg administered every 2 weeks. METHOD: After achieving stabilization with one of the doses, nine patients with a diagnosis of schizophrenia or schizoaffective disorder underwent [(11)C]raclopride PET to measure D(2) occupancy. Participants were scanned twice during the 2-week injection interval: within 3 days after injection (postinjection) and within 5 days before the next injection (preinjection). At the same time, plasma was collected for measurements of risperidone plus 9-hydroxyrisperidone. RESULTS: Mean post- and preinjection D(2) occupancy levels for the 25-, 50-, and 75-mg doses were 71.0% and 54.0%, 74.4% and 65.4%, and 81.5% and 75.0%, respectively. There was a significant correlation between dose and plasma concentrations of risperidone plus 9-hydroxyrisperidone, and the estimated plasma concentration associated with 50% D(2) occupancy (ED(50)) was 11.06 ng/ml. Prolactin levels were not correlated with drug levels or D(2) occupancy. CONCLUSIONS: All three doses of injectable risperidone showed peak D(2) occupancy levels above the 65% threshold associated with optimal clinical response; the 75-mg dose approximated the 80% threshold linked to increased risk of extrapyramidal symptoms. Doses of 25 or 50 mg should provide therapeutic efficacy while minimizing the risk of extrapyramidal symptoms.

Adult↗
PubMed2006

Insulin resistance and adiponectin levels in drug-free patients with schizophrenia: A preliminary report.

OBJECTIVE: To compare the insulin sensitivity and adiponectin levels of medication-free patients suffering from schizophrenia or schizoaffective disorder with that of matched healthy volunteers. METHOD: We evaluated 9 nondiabetic patients aged 26.6 years (median 26 years, range 17 to 41 years) and matched volunteers, using the frequently sampled intravenous glucose tolerance test, minimal model analysis, and fasting adiponectin levels. RESULTS: The mean insulin sensitivity index of the patients was 42% lower than that of the healthy volunteers (P = 0.026), with inadequate compensation in insulin secretion. Patients with schizophrenia tended to have reduced adiponectin levels (P = 0.055). CONCLUSIONS: By direct measurement, this study provides evidence of insulin resistance and susceptibility to type 2 diabetes in patients with schizophrenia who are free of antipsychotic drugs.

Adiponectin↗
PubMed2005

Validation of a physical activity assessment tool for individuals with schizophrenia.

OBJECTIVE: Increasing physical activity must be one component of lifestyle interventions designed to prevent or treat obesity in schizophrenia and there is now a need to develop low cost, practical and accurate measures of physical activity in this population to identify the prevalence of physical (in)activity and to assess the effectiveness of physical activity interventions. The objective of this study was to provide preliminary validation of the Short-Form International Physical Activity Questionnaire (IPAQ), a measurement tool that could prove useful for both clinicians and researchers in the field. METHOD: Reliability and validity data were collected from a sample of 35 outpatients with a DSM-IV diagnosis of schizophrenia. Test-retest repeatability was assessed within the same week and criterion validity was assessed against an RT3 accelerometer. Spearman's correlation coefficients are reported based on the total reported physical activity (minutes) and estimated energy expenditure. RESULT: We found a correlation coefficient of 0.68 for reliability and 0.37 for criterion validity based on total reported minutes of physical activity. There was a nonsignificant correlation (0.30; p>0.05) between the RT3 data and estimated energy expenditure derived from the IPAQ. CONCLUSION: Although not without limitations, the Short-Form IPAQ, when used with individuals with schizophrenia, exhibits measurement properties that are comparable to those reported in the general population and can be considered as a surveillance tool to assess levels of physical activity.

Adult↗
PubMed2005

Association study between a functional glutathione S-transferase (GSTP1) gene polymorphism (Ile105Val) and tardive dyskinesia.

A possible role for oxidative stress in the pathophysiology of tardive dyskinesia (TD) has previously been proposed (reviewed in Andreassen and Jorgensen [O.A. Andreassen, H.A. Jorgensen, Neurotoxicity associated with neuroleptic-induced oral dyskinesias in rats Implications for tardive dyskinesia? Prog. Neurobiol. 61 (2000) 525-541]). Long-term administration of antipsychotics alters dopaminergic turnover, which results in increased formation of reactive oxygen species (ROS). This is hypothesized to lead to TD through neuronal toxicity as a consequence of oxidative stress. In the present study, the relationship between TD and a functional polymorphism of the gene coding for human glutathione S-transferase P1 (GSTP1), an important antioxidant enzyme involved in the detoxification of ROS, was studied in 225 chronic treatment-refractory patients with schizophrenia. An isoleucine (Ile) to valine (Val) substitution at codon 105 (Ile105Val) in the GSTP1 gene was genotyped. No significant difference in total AIMS scores was found among patients in the three genotype groups (chi(2)=1.47, d.f.=2, p=0.48). Moreover, no significant differences in genotype (chi(2)=0.05, d.f.=2, p=0.98) or allele frequencies (chi(2)=0.00, d.f.=1, p=1.00) were observed between subjects with and without TD. Our results suggest that the GSTP1 gene polymorphism does not confer increased susceptibility to TD, although further studies are warranted before a conclusion can be drawn.

Adolescent↗
PubMed2005

Psychometric evaluation of the Readiness for Discharge Questionnaire.

OBJECTIVE: The Readiness for Discharge Questionnaire (RDQ) was developed as an easy to use tool for assessing readiness for discharge, independent of socio-economic factors, for inpatients with schizophrenia. The psychometric properties of the RDQ are described. METHODS: The RDQ consists of 6 items assessing suicidality/homicidality, control of aggression/impulsivity, activities of daily living, medication-taking, delusions/hallucinations interfering with functioning and global status. A final yes/no question assesses readiness for discharge. Data derived from 3 studies (500 patients in 3 countries) were used in analyzing inter-rater and test-retest reliability, content and construct validity, and sensitivity to change. RESULTS: The inter-rater reliability was high for all items of the RDQ (reliability coefficients >0.9) and moderate to high for the readiness for discharge status (Session I: 84% agreement, kappa 0.39, polychoric correlation r=0.81; Session II: 89% agreement, kappa 0.63, polychoric correlation r=0.81. Test-retest reliability was also high for all items of the RDQ (reliability coefficients >0.9) and the readiness for discharge status (kappa=0.743; tetrachoric correlation r=0.819). Overall, 84% of the raters agreed (mean score=5.0 of possible 6.0) that the RDQ was useful in assessing a patient's readiness for discharge from the hospital. Evidence of good construct validity included significant correlations with PANSS total and factor scores, and a significant relationship with actual discharge. Significantly more patients with symptom improvement were judged ready for discharge (compared to those without symptom improvement), indicating that the RDQ was sensitive to change over time. CONCLUSIONS: The RDQ has favorable reliability and validity properties, and is an easy to use instrument in research studies for assessing readiness for discharge of inpatients with schizophrenia. Additional work in naturalistic settings is required to further validate the instrument for routine clinical use.

Activities of Daily Living↗
PubMed2005

The crossover approach to switching antipsychotics: what is the evidence?

Clinicians frequently use a crossover approach in switching antipsychotics, although historically there has been a lack of data addressing the question of switch strategies. To establish if there is now empiric evidence that may guide clinicians in this regard, a MEDLINE search to April 2004 was carried out to identify published, randomized and controlled trials that have addressed this topic. A total of 404 articles were identified in the search, which resulted in the identification of four reports meeting the criteria. The four studies evaluated switching strategies to one of three atypical antipsychotics: aripiprazole, olanzapine (two reports), and ziprasidone. The switching process itself could be subdivided as follows: discontinuation (abrupt vs. gradual); and, replacement (abrupt vs. gradual). Meta-analyses confirmed a lack of difference in outcome, regardless of approach. While a crossover approach does not appear to increase adverse events, the available empiric evidence does not support its clinical superiority on various outcome measures. The existing data therefore argue against the position that a crossover approach in switching antipsychotics represents a 'safer' means of preventing clinical deterioration during the switch.

Antipsychotic Agents↗
PubMed2005

Predictors and markers of clozapine response.

RATIONALE: With other atypical antipsychotics now available, having predictors of clozapine response would be of considerable value, offering clinicians guidance in their decision as to when, and if, a trial of clozapine is warranted. OBJECTIVES: The aim was to review existing evidence regarding identified predictors and markers of clozapine response. METHODS: Relevant studies were identified through PUBMED searches (1975-June 2004) and cross-referencing of reviews and included studies. The data were summarized under two main categories: clinical (general, neurological, cognitive/neuropsychological, clozapine levels) and biological (biochemical, endocrine, genetic, metabolic, morphological, dopamine D2 receptor occupancy). 'Reliable' predictors/markers were defined a priori as those with support of at least two independent reports that addressed overall response, with no contradictory findings to date. 'Potential' predictors/markers had the support of a single report that addressed overall response and at least one other evaluating treatment outcome but not directly addressing response status. RESULTS AND CONCLUSIONS: Higher baseline clinical symptoms and functioning in the previous years and low cerebrospinal homovanillic acid/5-hydroxyindoleacetic acid levels were identified as reliable. Three potential measures were identified: reduction of frontal cortex metabolic activity, reduction of caudate volume, and improvement in P50 sensory gating.

Animals↗
PubMed2005

Continuous but not intermittent olanzapine infusion induces vacuous chewing movements in rats.

BACKGROUND: Continuous, but not intermittent, infusion with a conventional antipsychotic (haloperidol, HAL) can induce the vacuous chewing movement (VCM) syndrome in rats. The objective of this study was to determine whether continuous, versus intermittent, olanzapine (OLZ) infusion differently affects the development of VCMs. METHODS: Experiment 1: Animals were treated with 7.5 mg/kg/day of OLZ or vehicle (VEH) via either minipump (MP) or daily subcutaneous (SC) injections for 8 weeks. Experiment 2: A separate group of rats were treated with 15 mg/kg/day of OLZ, or 1 mg/kg/day of HAL or VEH via MP for 8 weeks. Dopamine D2 receptor occupancy levels were measured, ex vivo, with [3H]-raclopride. RESULTS: Experiment 1: Rats receiving 7.5 mg/kg/day of OLZ via MP (51% D2 occupancy), but not those receiving the same dose via daily SC injections (94% peak D2 occupancy), showed significant VCM levels compared with control animals (p = .02). Experiment 2: Both OLZ (67% D2 occupancy) and HAL (79% D2 occupancy) led to similar increases in VCMs compared with VEH (p = .005). CONCLUSIONS: This study provides strong evidence that even an atypical antipsychotic like OLZ, which rarely gives rise to tardive dyskinesia in the clinic, can lead to the VCM syndrome in rats if the antipsychotic is administered in a method (via MP) that leads to continuous presence of the drug in the brain.

Analysis of Variance↗