ABSTRACT
Risperidone is commonly used to treat different psychiatric disorders worldwide. Knowledge on dose-concentration relationships of risperidone treatment in children and adolescents with schizophrenia or other psychotic disorders is, however, scarce and no age-specific therapeutic ranges have been established yet. Multicenter data of a therapeutic drug monitoring service were analyzed to evaluate the relationship between risperidone dose and serum concentration of the active moiety (risperidone (RIS) plus its main metabolite 9-hydroxyrisperidone (9-OH-RIS)) in children and adolescents with psychotic disorders. Patient characteristics, doses, serum concentrations and therapeutic outcomes were assessed by standardized measures. The study also aimed to evaluate whether the therapeutic reference range for adults (20-60 ng/ml) is applicable for minors. In the 64 patients (aged 11-18 years) included, a positive correlation between daily dose and the active moiety (RISam) concentration was found (rs = 0.49, p = 0.001) with variation in dose explaining 24% (rs2 = 0.240) of the variability in serum concentrations. While the RISam concentration showed no difference, RIS as well 9-OH-RIS concentrations and the parent to metabolite ratio varied significantly in patients with co-medication of a CYP2D6 inhibitor. Patients with extrapyramidal symptoms (EPS) had on average higher RISam concentrations than patients without (p = 0.05). Considering EPS, the upper threshold of the therapeutic range of RISam was determined to be 33 ng/ml. A rough estimation method also indicated a possibly decreased lower limit of the preliminary therapeutic range in minors compared to adults. These preliminary data may contribute to the definition of a therapeutic window in children and adolescents with schizophrenic disorders treated with risperidone. TDM is recommended in this vulnerable population to prevent concentration-related adverse drug reactions.
Subject(s)
Antipsychotic Agents , Basal Ganglia Diseases , Psychotic Disorders , Schizophrenia , Adolescent , Adult , Antipsychotic Agents/adverse effects , Basal Ganglia Diseases/chemically induced , Child , Drug Monitoring , Humans , Paliperidone Palmitate/therapeutic use , Psychotic Disorders/drug therapy , Risperidone/therapeutic use , Schizophrenia/drug therapyABSTRACT
INTRODUCTION: Information about therapeutic serum levels of fluoxetine (FLX) and its major metabolite norfluoxetine (NORFLX) in children and adolescents is scarce. METHODS: Therapeutic drug monitoring (TDM) of FLX was routinely performed in 71 subjects treated for a major depressive disorder (MDD) (10-60 mg/d FLX, median: 20 mg/d). Correlations between serum concentration and dosage, age, gender, smoking habits and adverse events were analysed. RESULTS: Serum concentrations of the active moiety (FLX + NORFLX) ranged from 21 to 613 ng/mL (mean concentration of 213 ± 118 ng/mL, median: 185 ng/mL). High inter-individual variability in serum concentrations of the active moiety of FLX at each dosage level was observed and no relationship between serum concentration and clinical outcome was found. Apart from smoking, none of the factors tested had a significant eff ect on the serum concentration. DISCUSSION: It was shown that serum concentrations of the active moiety of FLX in children and adolescents seem to be similar to those in adults, with a high level of inter-individual variation. The proportion of patients who showed benefits from treatment with a dose of 20 mg/d FLX was high.
Subject(s)
Depressive Disorder, Major/drug therapy , Drug Monitoring/statistics & numerical data , Fluoxetine/pharmacokinetics , Fluoxetine/therapeutic use , Selective Serotonin Reuptake Inhibitors/pharmacokinetics , Selective Serotonin Reuptake Inhibitors/therapeutic use , Adolescent , Age Factors , Child , Cohort Studies , Depressive Disorder, Major/blood , Depressive Disorder, Major/psychology , Dose-Response Relationship, Drug , Drug Monitoring/methods , Feasibility Studies , Female , Fluoxetine/adverse effects , Fluoxetine/analogs & derivatives , Fluoxetine/blood , Humans , Male , Selective Serotonin Reuptake Inhibitors/adverse effects , Selective Serotonin Reuptake Inhibitors/blood , Sex Characteristics , Smoking/psychology , Young AdultABSTRACT
OBJECTIVES: Proteomic technologies based on mass spectrometry are increasingly used as a valuable tool in clinical research allowing high-throughput protein and peptide profiling to be undertaken. Whilst previous research has focussed the application of this novel technology on the study of patients with disorders compared to comparable individuals from the healthy population, this current study seeks to determine the effect of successful treatment for alcoholism on the serum protein profile obtained. METHODS: Serum samples were collected from patients after initial treatment for alcohol abuse and also 6 months after treatment. The serum samples were prepared for analysis using reverse phase magnetic bead fractionation and the resulting peptides analysed by matrix assisted laser desorption ionisation time-of-flight (MALDI-ToF) mass spectrometry. RESULTS: Whilst the majority of the peptides detected by this approach exhibited constant levels between the two time points, three peptides were elevated at the 6-month time point compared to the initial sampling. CONCLUSIONS: Whilst disorders with very clear biological causes (such as cancer) exhibit significantly different peptide profiles, psychiatric disorders such as alcohol addiction which are multifactorial show less obvious changes. Despite this the two groups of samples could statistically be distinguished by certain peptides expression levels.
Subject(s)
Alcoholism/blood , Blood Proteins/analysis , Protein Array Analysis/methods , Proteomics/methods , Smoking Cessation , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Tobacco Use Disorder/blood , Adult , Alcoholism/rehabilitation , Biomarkers/blood , Female , Humans , Magnetics , Male , Peptides/blood , Pilot Projects , Substance Abuse Treatment Centers , Tobacco Use Disorder/rehabilitation , Treatment OutcomeABSTRACT
INTRODUCTION: The aim of this prospective naturalistic study was to examine for the first time the relationship between dosage, serum concentration and clinical outcome in children and adolescents with impulsive-aggressive symptoms during risperidone therapy. METHODS: Steady state trough serum concentrations of risperidone and 9-hydroxyrisperidone (the active moiety) were measured in 103 subjects. The therapeutic effect was assessed by the clinical global impression improvement subscale and side effects by the Udvalg for Kliniske Undersogelser-side effect rating scale. RESULTS: We found a linear relationship between the risperidone dose and the serum concentration of the active moiety (Spearman rho=0.53) and no correlation between the serum concentration and either the therapeutic effect or side effects. There was no effect of gender and co-medication. DISCUSSION: This study has the typical limitations of naturalistic studies, therefore our results should be interpreted with caution. Based on the serum concentrations at the therapeutically effective dose range (0.25-1.5 mg/day) we obtained first information on a possibly appropriate therapeutic serum range for the risperidone treatment of children and adolescents with impulsive-aggressive symptoms. Further studies with greater sample sizes are needed to validate our results and to examine the influence of genetic polymorphisms on the serum concentration of risperidone.