RESUMO
Metformin (850-1700 mg) plus sibutramine (10-20 mg, n=13) or placebo (n=15) was administered for 12 weeks in olanzapine-treated chronic schizophrenia patients. Weight loss was similar in both groups: -2.8+/-3.2 kg vs. -1.4+/-2.6 kg. Except for preventing a triglyceride increase, the drug combination lacked efficacy for metabolic control in this clinical population.
Assuntos
Antipsicóticos/efeitos adversos , Depressores do Apetite/uso terapêutico , Benzodiazepinas/efeitos adversos , Ciclobutanos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/tratamento farmacológico , Metformina/uso terapêutico , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/uso terapêutico , Benzodiazepinas/uso terapêutico , Índice de Massa Corporal , Doença Crônica , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Olanzapina , Projetos Piloto , Placebos , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Relação Cintura-Quadril , Aumento de Peso/efeitos dos fármacos , Redução de Peso/efeitos dos fármacosRESUMO
Melkersson proposed leptin dysregulation as a factor in the olanzapine-induced metabolic dysfunction. Their suggestion was based on the absence of the expected positive correlation between serum leptin levels and the BMI, and the loss of the sex-dependent difference in leptin levels, which are higher in women. Although subsequent studies did not confirm that proposal, few of them assessed basal leptin levels and corrected for body fat percentage. Along with these variables, we added a precise definition of participants out of the expected positive correlation in a large sample of schizophrenia patients. Sixty patients (26 women and 34 men) with severe schizophrenia undergoing chronic hospitalization and conventional antipsychotic treatment were switched to olanzapine (10-20 mg/day). We assessed at baseline, and at weeks 8 and 16 of treatment, the percentage of participants with abnormal correlation (out of the 95% confidence interval in the regression line) between leptin levels and the BMI, and the correlation between leptin and insulin, glucose, the insulin resistance index, c-reactive protein (CRP) and treatment response. Leptin levels were higher in women than in men (P<0.01). The positive correlation between leptin levels, BMI and percentage of fat were preserved. After olanzapine, 3.8% of women and 2.9-5.8% of men were out the 95% confidence interval, and the proportion was similar at baseline. Glucose, insulin, the insulin resistance index and the CRP levels significantly increased after olanzapine. The impact of olanzapine on leptin regulation appears discrete and limited to a small number of participants. Additional studies must clarify the features that render them to metabolic dysregulation.
Assuntos
Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Índice de Massa Corporal , Leptina/sangue , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/farmacologia , Benzodiazepinas/efeitos adversos , Benzodiazepinas/farmacologia , Benzodiazepinas/uso terapêutico , Glicemia/efeitos dos fármacos , Proteína C-Reativa/análise , Feminino , Humanos , Insulina/sangue , Resistência à Insulina , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Olanzapina , Fatores Sexuais , Aumento de Peso/efeitos dos fármacosRESUMO
BACKGROUND: Excessive body weight gain (BWG) is a clinically relevant side effect of olanzapine administration. The primary objective of this study was to assess whether metformin prevents or reverses BWG in patients with schizophrenia or bipolar disorder under olanzapine administration. Secondarily we evaluated diverse metabolic variables. METHODS: Eighty patients taking olanzapine (5-20 mg daily for more than 4 consecutive months) were randomly allocated to metformin (n=40; 850 to 2550 mg daily) or placebo (n=40) group in a 12-week double-blind protocol. Waist circumference (WC) body weight (BW), body mass index (BMI) fasting glucose, glycated hemoglobin (Hb1c), insulin, an insulin resistance index (HOMA-IR) lipids, leptin, c-reactive protein, fibrinogen, cortisol and the growth hormone (GH) were evaluated at baseline and at week 12 of treatment. RESULTS: The metformin group lost 1.4+/-3.2 kg (p=0.01) and tended to decrease its leptin levels, whereas the placebo group maintained a stable weight: -0.18+/-2.8 kg (p=0.7). The HOMA-IR significantly increased after placebo (p=0.006) and did not change after metformin (p=0.8). No ostensible differences were observed in the other variables, even though metformin did not improve the lipid profile and the Hb1c levels. CONCLUSIONS: Metformin may safely assist olanzapine-treated patients in body weight and carbohydrate metabolism control.