RESUMEN
OBJECTIVE: Treatment with most antipsychotics is associated with an increased risk of weight gain and metabolic disturbances. In a randomized trial, we previously demonstrated that 16 weeks of glucagon-like peptide-1 receptor agonist liraglutide treatment vs. placebo significantly reduced glucometabolic disturbances and body weight in prediabetic, overweight/obese schizophrenia-spectrum disorder patients treated with clozapine or olanzapine. The aim of this study was to investigate whether the beneficial effects of the 16-week intervention were sustained beyond the intervention period. METHOD: One year after completion of the intervention, we investigated changes in body weight, fasting glucose, glycated hemoglobin, C-peptide, and lipids comparing 1-year follow-up levels to end of treatment (week 16) and baseline (week 0) levels. RESULTS: From end of treatment to the 1-year follow-up, body weight had increased in the liraglutide-treated group. However, compared to baseline levels, the placebo-subtracted body weight loss remained significantly reduced (-3.8 kg, 95% CI: -7.3 to -0.2, P = 0.04). Fasting glucose, glycated hemoglobin, C-peptide, and lipids had each returned to baseline levels 1 year after stopping liraglutide. CONCLUSION: The body weight reduction during 16 weeks of liraglutide treatment was partially sustained 1 year after the intervention was completed. However, the improvements in other metabolic parameters returned to baseline levels.
Asunto(s)
Hipoglucemiantes/farmacología , Liraglutida/farmacología , Obesidad/tratamiento farmacológico , Sobrepeso/tratamiento farmacológico , Estado Prediabético/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antipsicóticos/efectos adversos , Antipsicóticos/uso terapéutico , Glucemia/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Péptido C/efectos de los fármacos , Clozapina/efectos adversos , Clozapina/uso terapéutico , Dinamarca/epidemiología , Ayuno , Femenino , Estudios de Seguimiento , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hemoglobina Glucada/efectos de los fármacos , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Metabolismo de los Lípidos/efectos de los fármacos , Liraglutida/administración & dosificación , Liraglutida/uso terapéutico , Masculino , Persona de Mediana Edad , Obesidad/inducido químicamente , Obesidad/epidemiología , Olanzapina/efectos adversos , Olanzapina/uso terapéutico , Sobrepeso/inducido químicamente , Sobrepeso/epidemiología , Placebos/administración & dosificación , Estado Prediabético/inducido químicamente , Estado Prediabético/epidemiología , Esquizofrenia/sangre , Esquizofrenia/diagnóstico , Esquizofrenia/tratamiento farmacológico , Adulto JovenAsunto(s)
Agranulocitosis/inducido químicamente , Antipsicóticos/efectos adversos , Clozapina/efectos adversos , Eosinófilos/efectos de los fármacos , Esquizofrenia/sangre , Esquizofrenia/tratamiento farmacológico , Adulto , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Caracteres Sexuales , Factores SexualesRESUMEN
OBJECTIVE: Therapeutic drug monitoring (TDM) of clozapine is standardized to 12-h postdose samplings. In clinical settings, sampling time often deviates from this time point, although the importance of the deviation is unknown. To this end, serum concentrations (s-) of clozapine and its metabolite N-desmethyl-clozapine (norclozapine) were measured at 12 ± 1 and 2 h postdose. METHOD: Forty-six patients with a diagnosis of schizophrenia, and on stable clozapine treatment, were enrolled for hourly, venous blood sampling at 10-14 h postdose. RESULTS: Minor changes in median percentage values were observed for both s-clozapine (-8.4%) and s-norclozapine (+1.2%) across the 4-h time span. Maximum individual differences were 42.8% for s-clozapine and 38.4% for s-norclozapine. Compared to 12-h values, maximum median differences were 8.4% for s-clozapine and 7.3% for s-norclozapine at deviations of ±2 h. Maximum individual differences were 52.6% for s-clozapine and 105.0% for s-norclozapine. The magnitude of s-clozapine differences was significantly associated with age, body mass index and the presence of chronic basophilia or monocytosis. CONCLUSION: The impact of deviations in clozapine TDM sampling time, within the time span of 10-14 h postdose, seems of minor importance when looking at median percentage differences. However, substantial individual differences were observed, which implies a need to adhere to a fixed sampling time.