Metformin plus sibutramine for olanzapine-associated weight gain and metabolic dysfunction in schizophrenia: a 12-week double-blind, placebo-controlled pilot study.

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.

Metformin as an adjunctive treatment to control body weight and metabolic dysfunction during olanzapine administration: a multicentric, double-blind, placebo-controlled trial.

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.

Similar frequency of abnormal correlation between serum leptin levels and BMI before and after olanzapine treatment in schizophrenia.

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.

Insulin counter-regulatory factors, fibrinogen and C-reactive protein during olanzapine administration: effects of the antidiabetic metformin.

In this study, the Authors assessed some insulin counter-regulatory factors, fibrinogen and C-reactive protein after olanzapine administration, and the effect of metformin on these variables, 37 patients with chronic schizophrenia were given olanzapine (10 mg/day for 14 weeks). Nineteen patients received metformin (850-2550 mg/day) and 18 received placebo in a randomized, double-blind protocol. The following variables were quantified before and after olanzapine: cortisol, leptin, tumor necrosis factor-alpha, glucagon, growth hormone, fibrinogen and C-reactive protein. Results were correlated with the changes in body weight and the insulin resistance index. We have reported elsewhere that metformin did not prevent olanzapine-induced weight gain, and the insulin resistance index significantly decreased after metformin and placebo; Baptista T, et al. Can J Psychiatry 2006; 51: 192-196. Cortisol, tumor necrosis factor-alpha and fibrinogen levels significantly decreased in both groups. Glucagon significantly increased after metformin (P=0.03). Leptin tended to increase after placebo (P=0.1) and displayed a small nonsignificant reduction after metformin. The C-reactive protein did not change significantly in any group. Contrarily to most published studies, olanzapine was associated with decreased insulin resistance. Decrements in cortisol, fibrinogen and tumor necrosis factor-alpha levels point to an improvement in the metabolic profile. The trend for leptin to increase after placebo, but not after metformin in spite of similar weight gain suggests a beneficial effect of this antidiabetic agent.

Cysticercosis in chronic psychiatric inpatients from a Venezuelan community.

Cysticercosis due to Taenia solium infection is endemic in developing countries of the Americas, Asia, and Africa. This study was designed to establish the prevalence of cysticercosis in 158 inpatients of a psychiatric institution in the state of Tachira (Venezuela) and in 127 healthy control subjects. Positive blood tests for cysticercosis by Western blotting were recorded in 18.35% of the patients and in 1.57% of the controls. Individuals with mental retardation were found to carry an increased risk of cysticercosis (RR: 2.92; 1.22 < 2.92 > 7.0; P < 0.05) compared with patients with other psychiatric disorders. Taeniasis by Taenia spp. was not demonstrated in the patient group, although a high incidence of infection by other helminths (95.1%) was detected. The high prevalence of cysticercosis in the psychiatric inpatient group, compared with healthy individuals, and the lack of a differential diagnosis of neurocysticercosis suggest cerebral cysticercosis in a large proportion of these patients. Cysticercosis could be the origin of the psychiatric disorders of these patients and may also be due to contact with the parasite in an environment with poor hygiene conditions and a deficient health care system.