RESUMO
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.
Assuntos
Hipoglicemiantes/farmacologia , Liraglutida/farmacologia , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Estado Pré-Diabético/tratamento farmacológico , Adolescente , Adulto , Idoso , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Peptídeo C/efeitos dos fármacos , Clozapina/efeitos adversos , Clozapina/uso terapêutico , Dinamarca/epidemiologia , Jejum , Feminino , Seguimentos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hemoglobinas Glicadas/efeitos dos fármacos , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Liraglutida/administração & dosagem , Liraglutida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Obesidade/induzido quimicamente , Obesidade/epidemiologia , Olanzapina/efeitos adversos , Olanzapina/uso terapêutico , Sobrepeso/induzido quimicamente , Sobrepeso/epidemiologia , Placebos/administração & dosagem , Estado Pré-Diabético/induzido quimicamente , Estado Pré-Diabético/epidemiologia , Esquizofrenia/sangue , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Adulto JovemRESUMO
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.