PubMed Health⌕ Search

Biomedical subjects

Christoph U Correll

Publications and source records attributed to Christoph U Correll.

At least 19 recordsLinked to original sources

Research agenda to advance anhedonia assessment, understanding and treatment: an ECNP-GALENOS expert meeting report.

Anhedonia, broadly defined as a reduced ability to experience interest or pleasure, represents an important transdiagnostic neuropsychiatric symptom dimension which may benefit from targeted diagnostics and treatments. Different lines of research have proposed that it comprises multiple facets, including deficits in anticipatory ('wanting') and consummatory ('liking') reward processing as well as reward learning and affects different aspects of life (eg, social, physical, cognitive). Certain facets-more specifically anticipation, motivation and reward learning-likely involve blunted phasic dopaminergic signalling. However, recent meta-analytical evidence of human depression studies indicates that prodopaminergic antidepressants produce relatively small improvements in anhedonia symptoms and suggest that mechanisms beyond dopamine likely contribute to anhedonia. This stimulated an expert meeting to review the literature and define priorities for future research in anhedonia. A central key priority is developing a translational biologically-informed nomenclature and consensus that solves the current mismatch between constructs, paradigms and measures, and mechanisms, which separates discrete reward-related processes such as effort allocation, reward learning and anticipatory interest versus consummatory pleasure. Clinical research priorities are improved multimodal measurement tools, integrating neurobiological frameworks (eg, neuroimaging, electrophysiology and liquid biomarkers capturing dopaminergic, glutamatergic, opioid and immunometabolic pathways) and transdiagnostic studies across neuropsychiatric disorders and developmental stages. Innovative trial designs that explicitly target anhedonic phenotypes as a primary outcome and test mechanism-based interventions are also needed. Translational research recommendations include back-translation strategies that begin with patient-relevant phenotypes followed by the development of comparable human and animal tasks that target reward-related processes, such as effort allocation, reward learning and anticipatory interest versus consummatory pleasure, improve cross-species behavioural paradigms and enhance methodological rigour and reproducibility. Collectively, these recommendations will help refine the conceptualisation of anhedonia and advance its role within precision psychiatry as a mechanistically grounded target across multiple disorders.

Humans↗

Characterization of local tolerability of TV-46000, a long-acting subcutaneous formulation of risperidone for the treatment of schizophrenia.

TV-46000 is a long-acting injectable antipsychotic (LAI) approved for the treatment of adults with schizophrenia and bipolar I disorder. LAIs like TV-46000 can improve adherence and reduce relapse in patients with schizophrenia; however, injection site reactions (ISRs) can contribute to LAI discontinuation. ISRs with TV-46000 treatment were characterized using data from two phase 3 trials of patients with schizophrenia (RISE [NCT03503318], SHINE [NCT03893825]) and a phase 1 study of patients with schizophrenia or schizoaffective disorder. Patients in the pooled safety population (aged 16-67 years) from RISE and SHINE (n = 525 TV-46000, n = 179 placebo) received 4554 TV-46000 injections and 2721 placebo injections. ISRs were reported in 19 % (n = 102) of patients who received TV-46000, corresponding to an exposure-adjusted event rate (EAER)/100 patient-years of 48.67. ISRs led to 9 (1.7 %) treatment discontinuations of TV-46000. The most frequently reported ISR adverse events were injection site pain (EAER, 15.38, n = 36 [7 %]) and injection site nodule (EAER, 12.01, n = 35 [7 %]). ISR frequency and pain and nodule adverse event frequency decreased after the first injection. In the phase 1 study (n = 99), mean injection site pain scores were highest immediately after injection, showed a notable decrease within 10 min of injection, and further decreased within 1 h after injection. In conclusion, for >4500 injections evaluated, ISR rates with TV-46000 were modest. Most ISRs were mild or moderate and rarely led to treatment discontinuation. Results support the favorable tolerability of TV-46000 as a treatment for schizophrenia in adults.

Humans↗

Improving access to antipsychotic medications for schizophrenia in Ethiopia, Nigeria, Rwanda, and South Africa: an evidence-based global consensus.

There are disparities in access to antipsychotics for schizophrenia across different country settings. Improving access to a wider and more equitable range of medications in low-income and middle-income countries is a priority. A multidisciplinary team of international experts, including individuals with lived experience, appraised the most relevant and recent information on antipsychotics in schizophrenia and contextualised it to four African countries (Ethiopia, Nigeria, Rwanda, and South Africa) using a validated consensus methodology. We recommended a list of drugs to prioritise to guide clinical implementation and research, and market shaping. We identified key evidence gaps: little of the existing evidence comes from the countries of interest, trials generally involve highly selected populations, and the complexity of real-world settings is not reflected. However, this methodology highlights a route forward to prioritise the best available evidence on pharmacological treatments for schizophrenia at a global scale, which could also be applied to treatments for other mental health conditions.

Humans↗

Does antipsychotic polypharmacy increase the risk for metabolic syndrome?

OBJECTIVE: To determine whether the coprescribing of two or more antipsychotics, a relatively frequent practice with little data to support its safety and efficacy, is associated with an increased prevalence of metabolic syndrome. METHODS: 364 newly admitted adults treated with second-generation antipsychotics underwent assessments evaluating antipsychotic polytherapy, and of the presence of metabolic syndrome and triglycerides/high-density lipoprotein cholesterol ratio>3.5 (TG/HDL), a sensitive marker of insulin resistance. The correlates of antipsychotic polytherapy and associations with metabolic syndrome and TG/HDL were determined by univariate comparisons and multiple logistic regression analyses. RESULTS: Antipsychotic polytherapy was present in 70 patients (19.2%) and was significantly more likely in patients with schizophrenia and those treated with clozapine, quetiapine or ziprasidone (p<0.0001). Compared with antipsychotic monotherapy, polytherapy was associated with elevated rates of metabolic syndrome (50.0% vs. 34.3%, p=0.015) and TG/HDL (50.7% vs. 35.0%, p=0.016). However, in logistic regression analyses, metabolic syndrome was significantly associated with higher body mass index (BMI), older age, a diagnosis of bipolar disorder or schizophrenia, and cotreatment with a first-generation antipsychotic (r(2): 0.25, p<0.0001). The TG/HDL marker of insulin resistance was associated with higher BMI, male sex, Caucasian race and absence of aripiprazole treatment (r(2): 0.14, p<0.0001). Antipsychotic polypharmacy dropped out of both multivariate models. CONCLUSIONS: Compared with patients receiving antipsychotic monotherapy, patients on antipsychotic polytherapy have higher rates of metabolic syndrome and lipid markers of insulin resistance. However, antipsychotic polytherapy is not independently associated with the prevalence of these abnormalities, which are related to known demographic, clinical and anthropometric risk factors.

Adult↗

Recognizing and monitoring adverse events of second-generation antipsychotics in children and adolescents.

Although second-generation antipsychotics (SGAs) are used increasingly in children and adolescents, data on the effectiveness and safety in pediatric populations are still sparse. Much of the safety information is derived from studies conducted in adults. This derivation is problematic because children and adolescents are exposed to SGAs during a phase of unparalleled physical and psychologic development that can affect pharmacokinetic and pharmacodynamic drug actions, efficacy, and side-effect patterns. This article presents an overview of SGA-related side effects in children and adolescents and strategies to monitor health outcomes effectively in youngsters receiving SGAs.

Adolescent↗

Endocrine and metabolic adverse effects of psychotropic medications in children and adolescents.

OBJECTIVE: Despite increasing use of psychotropic medications in children and adolescents, data regarding their efficacy and safety are limited. Endocrine and metabolic adverse effects are among the most concerning adverse effects of commonly used psychotropic medications. METHOD: Selective review of endocrine and metabolic effects of psychotropic medications in pediatric populations, with a focus on monitoring and management strategies. RESULTS: Because youth are still developing at the time of psychotropic drug exposure, most reference values need to be adjusted for gender and age. As in adults, youngsters receiving lithium require monitoring for thyroid dysfunction. Psychostimulants appear to cause mild reversible growth retardation in some patients, most likely because of decreased weight or slowing of expected weight gain; some patients may experience clinically significant reductions in adult height. Although still controversial, valproate use has been associated with an increased risk for polycystic ovary syndrome, in addition to causing weight gain. Although more data are required, children and adolescents appear to be at higher risk than adults for antipsychotic-induced hyperprolactinemia, weight gain, and possibly, associated metabolic abnormalities, which is of particular concern. CONCLUSIONS: Clinicians and caregivers need to be aware of potential endocrine and metabolic adverse effects of psychiatric medications. A careful selection of patients, choice of agents with potentially lesser risk for these adverse events, healthy lifestyle counseling, as well as close health monitoring are warranted to maximize effectiveness and safety.

Adolescent↗

Metabolic syndrome and the risk of coronary heart disease in 367 patients treated with second-generation antipsychotic drugs.

OBJECTIVE: To examine the relationship between presence of metabolic syndrome and the risk of coronary heart disease (CHD) events (angina pectoris, myocardial infarction, and sudden cardiac death) in patients treated with second-generation antipsychotic medications. METHOD: 367 adults treated with second-generation antipsychotics randomly selected from consecutive psychiatric admissions to a single hospital between August 1, 2004, and March 1, 2005, underwent assessments evaluating the presence of metabolic syndrome. The 10-year risk of CHD events was calculated according to the Framingham scoring system for age, smoking, total cholesterol, high-density lipoprotein (HDL)-cholesterol, blood pressure, and history of diabetes and was compared in patients with and without the metabolic syndrome. RESULTS: Metabolic syndrome, present in 137 patients (37.3%), was associated with a significantly greater age- and race-adjusted 10-year risk of CHD events, i.e., 11.5% vs. 5.3% for men (risk ratio = 2.18, 95% CI = 1.88 to 2.48, p < .0001) and 4.5% vs. 2.3% for women (risk ratio = 1.94, 95% CI = 1.65 to 2.23, p = .0005). The increased risk of CHD events in patients with metabolic syndrome remained significant after the exclusion of diabetic patients. In a logistic regression analysis of variables independent of the Framingham scoring system, triglyceride levels (p < .0001), waist circumference (p = .035), and white race (p = .047) were significantly associated with the 10-year risk of CHD events (R2 = 0.134; p < .0001). CONCLUSIONS: These data confirm the high prevalence of metabolic syndrome in patients receiving second-generation anti-psychotics, indicate that metabolic syndrome doubles the 10-year risk of CHD events in this population, and emphasize the importance of the "hypertriglyceridemic waist" for the identification of psychiatric patients at high risk of CHD.

Adult↗

Prospective study of adolescents with subsyndromal psychosis: characteristics and outcome.

OBJECTIVE: The aim of this study was to examine the characteristics and outcome of adolescents with psychotic disorder not otherwise specified (PsyNOS) and brief psychotic disorder (BrPsy), two neglected subsyndromal diagnostic entities. METHODS: As part of an ongoing, naturalistic study investigating adolescents considered to be prodromal for schizophrenia, 29 youngsters (mean age, 16.2 +/- 2.7 years) with PsyNOS or BrPsy were identified as theoretically at highest risk for schizophrenia and followed for over 6 (mean, 22.8 +/- 19.4) months. RESULTS: Contrary to our expectations, only 7 of the 26 individuals (27.0%) with follow-up data developed schizophrenia or schizoaffective disorder, and only 2 subjects (7.7%) retained their diagnosis of BrPsy/PsyNOS. The most frequent other diagnoses at follow-up were mood disorders (34.6%), personality disorders (11.5%), and obsessive-compulsive disorder (7.7%). Regarding severity of outcome, 38.5% of the patients progressed to a syndromal psychotic disorder, 23.1% continued to have attenuated positive symptoms, and 38.4% improved to having attenuated negative symptoms only, or no positive or negative symptoms. BrPsy was associated with lower maximum levels of negative symptoms (p = 0.02) and higher likelihood of symptom remission (p = 0.02). CONCLUSIONS: This study indicates that psychotic symptoms not fulfilling criteria for schizophrenia or a psychotic mood disorder are unreliable predictors of a syndromal psychotic disorder outcome at 2 years. Long-term studies of PsyNOS and BrPsy are needed to clarify where these disorders fall in the developmental course of schizophrenia.

Adolescent↗

Cost-effective screening for the metabolic syndrome in patients treated with second-generation antipsychotic medications.

OBJECTIVE: Despite concerns about the adverse effects of second-generation antipsychotics on weight regulation and glucose and lipid metabolism, little is known about the relationship between these agents and the metabolic syndrome. Because the metabolic syndrome is more strongly associated with cardiovascular morbidity and mortality than its individual components, attention to the full syndrome is important. The authors' goal was to explore the relationship between second-generation antipsychotics and the metabolic syndrome. METHOD: They assessed the prevalence of metabolic syndrome in a nearly consecutive group of 89 acutely admitted psychiatric inpatients treated with at least one second-generation antipsychotic for different psychiatric disorders. Patients' waist circumference and blood pressure were measured as well as their fasting blood glucose and lipid levels. RESULTS: Twenty-six (29.2%) of the 89 patients fulfilled criteria for the metabolic syndrome. Presence of the syndrome was associated with older age, higher body mass index, and higher values for each individual criterion of the metabolic syndrome but not with specific diagnoses or antipsychotic treatment regimens. Presence of abdominal obesity was most sensitive (92.0%), while fasting glucose >110 mg/dl was most specific (95.2%) in correctly identifying the presence of metabolic syndrome. Combining abdominal obesity and elevated fasting blood glucose had 100% sensitivity. CONCLUSIONS: The measurement of both abdominal obesity and fasting blood glucose is a simple, cost-effective screening test to detect patients at high risk for future cardiovascular morbidity.

Adolescent↗

Pharmacogenetics of antipsychotic-induced weight gain.

RATIONALE: Antipsychotic medications have been associated with considerable weight gain. The degree of inter-individual variability and known genetic contributions to obesity suggest a combination of genetic and environmental factors. In the absence of established mechanisms and valid predictors for this relevant adverse effect, pharmacogenetic studies may provide the basis for the development of individualized treatment and preventive interventions. OBJECTIVE: The aim of the present review is to analyze the theoretical and empirical knowledge base for the selection of the most promising target genes that may contribute to antipsychotic-induced weight gain. METHODS: Examination of the preclinical and clinical literature that can inform the rational choice of target genes that may play a role in the development of adverse changes in body composition associated with antipsychotic treatment. RESULTS: Theoretically, candidate gene selection can be guided by knowledge about molecular pathways associated with obesity, receptors modulated by antipsychotic drugs, and enzymes implicated in their metabolism and bioavailability. While most available data relate to the general mechanisms of obesity and few studies have directly examined the genetic contributions to antipsychotic-induced weight gain, several genes warrant further investigation. These include the 5-HT(2C), pro-opiomelanocortin, leptin, ghrelin, tumor necrosis factor alpha, adiponectin, dopamine D(2) receptor, histamine-H(1) receptor, and alpha(1), beta(2) and beta(3) adrenergic receptor genes. CONCLUSIONS: Pharmacogenetic studies can provide powerful tools for the pre-treatment identification of individuals at high risk for antipsychotic-induced weight gain, to uncover biological mechanisms that may even generalize to non-drug-induced weight gain, and to isolate novel targets for treatments of weight gain and obesity. To enhance power, future studies should pay close attention to population selection and avoidance/control of confounds, particularly past treatment exposure.

Adiponectin↗

Nonspecific and attenuated negative symptoms in patients at clinical high-risk for schizophrenia.

BACKGROUND: Retrospective studies have shown that nonspecific psychopathology and negative symptoms, including social isolation and academic dysfunction, tend to precede onset of psychosis. The present report describes the baseline psychopathology of subjects in the Hillside Recognition and Prevention (RAP) Program, and presents an operationalized classification algorithm for the prospective study of both positive and negative symptoms of clinical high-risk (CHR) for schizophrenia. METHODS: Eighty-two adolescent and young adult patients were characterized using semi-structured interviews of both a parent informant and the patient. The Scale of Prodromal Symptoms (SOPS) was utilized to derive a three-part classification scheme: CHR- subjects (n=20) were defined as having at least one attenuated negative symptom with no positive symptoms; CHR+ subjects (n=42) were defined as having one or more attenuated positive symptoms without psychosis; schizophrenia-like psychosis (SLP) subjects (n=20) were defined as having a psychotic symptom, but without meeting criterion A, B, or C of DSM-IV schizophrenia. RESULTS: Social isolation was the most common presenting symptom. The three RAP subgroups did not significantly differ in levels of attenuated negative and disorganized symptoms, despite the fact that these were not required for inclusion in the CHR+ and SLP groups. Common co-morbid diagnoses included major depression, attention deficit hyperactivity disorder, avoidant personality disorder, and Cluster A personality disorders. CONCLUSIONS: Negative symptoms and other nonspecific behavioral abnormalities represent clinically important phenomena in prodromal patients, and may provide insight into pathophysiologic mechanisms in schizophrenia and possible preventive interventions.

Adolescent↗

Determination of plasma ziprasidone using liquid chromatography with fluorescence detection.

A liquid chromatographic procedure was developed for the determination of a new antipsychotic agent ziprasidone in plasma using fluorescence detection. A one-step liquid-liquid extraction from 1 ml of alkalinized plasma containing an internal standard alpha-ergocryptine using methyl-t-butyl ether afforded a greater than 84% recovery of ziprasidone. Chromatography was performed using a reversed-phase trimethylsilyl bonded silica column with a mobile phase of 72:28 phosphate buffer:acetonitrile at a flow rate of 1.5 ml/min. Detection of the eluted peaks was observed using excitation and emission wavelengths of 320 and 410 nm, respectively. Chromatographic run time did not exceed 14 min with no interference from endogenous material. The calibration curve was linear over the concentration range of 0.5 to 200 ng/ml and the inter- and intra-assay imprecision (CV) was less than 10%. The lower limit of quantitation was assessed at 0.5 ng/ml. Specificity of the method is demonstrated by the lack of interference from a large number of commonly used drugs and their metabolites in clinical use. The utility of the method is exemplified with the presentation of clinical data from patients receiving ziprasidone.

Antipsychotic Agents↗

A prospective study of hyperprolactinemia in children and adolescents treated with atypical antipsychotic agents.

OBJECTIVE: Few studies have prospectively compared the change of prolactin levels in children and adolescents associated with the use of atypical antipsychotic agents. In our study, we present preliminary data of an ongoing study, which compares changes in prolactin levels in children and adolescents after treatment to risperidone versus olanzapine versus quetiapine. We hypothesized: (1) risperidone would be associated with hyperprolactinemia most frequently, and (2) postpubertal females may be at higher risk of prolactin elevation and associated adverse effects. METHODS: Prolactin levels were obtained at baseline and after a mean of 11.2 weeks (SD = 2.2; range, 4-15 weeks) from 40 subjects (mean age, 13.4 years; SD = 3.4; range, 5-18 years) who were started on risperidone (n = 21), olanzapine (n = 13), or quetiapine (n = 6). End-point prolactin levels were compared using a Kruskal-Wallis test. RESULTS: End-point prolactin levels were significantly higher with risperidone, compared to olanzapine (p = 0.027) or quetiapine (p = 0.008). With the Bonferroni correction, the latter remains significant. Twenty-five percent of our subjects experienced sexual side effects at end point, independent of prolactin levels and antipsychotic agents. CONCLUSION: Risperidone significantly increased prolactin levels in children and adolescents. The duration of this prolactin elevation, and its long-term effects in children and adolescents, are unknown.

Adolescent↗

Lower risk for tardive dyskinesia associated with second-generation antipsychotics: a systematic review of 1-year studies.

OBJECTIVE: Based on lower rates of acute extrapyramidal side effects associated with second-generation antipsychotics, compared to first-generation antipsychotics, and based on preliminary data, second-generation antipsychotics are expected to cause less tardive dyskinesia than first-generation antipsychotics. This hypothesis was examined in a systematic review of studies involving open or controlled treatment with any second-generation antipsychotic. METHOD: Studies of treatment with second-generation antipsychotics lasting > or =1 year and reporting on new cases of tardive dyskinesia or dyskinesia were systematically reviewed. RESULTS: In 11 studies, 2,769 patients received treatment with risperidone (five studies, N=1,235), olanzapine (two studies, N=610), quetiapine (two studies, N=386), amisulpride (one study, N=331), or ziprasidone (one study, N=207) for a weighted mean and median duration of 263 and 306 days, respectively. Study designs were double blind and randomized (N=3); open-label extensions of double-blind, randomized trials (N=4); and open label (N=4). Of the four trials that had a comparator (all involving adults with schizophrenia spectrum disorders), three used haloperidol (N=408) and one used placebo (N=71). Studied populations included children (N=77), adults (N=1,419), adults and elderly persons (N=794), and exclusively patients age 54 years or older (N=479). The weighted mean annual incidence of tardive dyskinesia for second-generation antipsychotics was 0% in the children, 0.8% (range=0.0%-1.5%) in the adults, 6.8% in the mixed adult and elderly population, and 5.3% (range=0.0%-13.4%) in the patients age 54 years and older, compared to 5.4% (range=4.1%-7.4%) in adults treated with haloperidol. CONCLUSIONS: Results from 11 long-term studies support the idea that second-generation antipsychotics have a reduced risk for tardive dyskinesia, compared to first-generation antipsychotics, although the doses of haloperidol used in the comparator studies were relatively high. More carefully designed studies, ideally lasting beyond 1 year and comparing the effects of different second-generation antipsychotics in patients who have never taken first-generation antipsychotics, are needed to estimate the true risk. It would not appear premature for clinicians to consider these findings in making long-term treatment decisions.

Adolescent↗