ABSTRACT
RATIONALE: Olanzapine (OLZ) is known to cause weight gain and metabolic disturbances, which may have serious implications with respect to medical comorbidities such as metabolic syndrome and insulin resistance. OBJECTIVES: The aim of this study was to evaluate the effects of two angiotensin II type 1 receptor blockers (ARBs) which are widely used as antihypertensive agents, valsartan (VAL) and telmisartan (TEL), on insulin resistance in patients with schizophrenia treated with OLZ. METHODS: Thirty inpatients with schizophrenia with OLZ monotherapy over 8 weeks participated in this study. To assess insulin resistance, the homeostasis model assessment of insulin resistance (HOMA-IR), fasting plasma glucose (PG) levels and immunoreactive insulin (IRI) levels were measured [HOMA-IR = fasting PG level (mmol/L) x fasting IRI level (µU/ml)/22.5]. VAL add-on treatment was performed in insulin-resistant patients (HOMA-IR > 1.6) for 12 weeks. After a 12-week VAL washout period, TEL add-on treatment was carried out for 12 weeks. The effects of ARBs on insulin resistance and other metabolic variables were assessed. RESULTS: In all 30 patients, both body mass index and abdominal circumference were strongly correlated with HOMA-IR. Twelve patients showed high HOMA-IR and were deemed to be insulin resistant. Add-on therapy of VAL and TEL resulted in a significant decrease in fasting IRI levels and HOMA-IR. No differences in any effects were observed between VAL and TEL. No adverse effects of either ARBs were observed in this study. CONCLUSIONS: ARBs for patients treated with OLZ improved insulin sensitivity and attenuated insulin resistance.
Subject(s)
Angiotensin II Type 1 Receptor Blockers/therapeutic use , Benzimidazoles/therapeutic use , Benzoates/therapeutic use , Benzodiazepines/adverse effects , Benzodiazepines/therapeutic use , Insulin Resistance , Schizophrenia/drug therapy , Tetrazoles/therapeutic use , Valine/analogs & derivatives , Antipsychotic Agents/adverse effects , Antipsychotic Agents/therapeutic use , Female , Humans , Hyperinsulinism/drug therapy , Insulin Resistance/physiology , Male , Middle Aged , Olanzapine , Receptor, Angiotensin, Type 1/physiology , Telmisartan , Valine/therapeutic use , ValsartanABSTRACT
Recent studies indicate that carbamazepine (CBZ) induces hepatic cytochrome p450 (CYP) protein subfamilies. The present study examines the time-course of the appearance of hepatic CYP subfamilies (2B, 3A) and serum levels of CBZ and its metabolite, CBZ epoxide (CBZE), induced by CBZ treatment in rats. Male Wistar rats were given 5 g of CBZ (CBZ-treated) per 1 kg of feed for 3, 7, 14, 28 and 42 d or feed without CBZ (control). Serum levels of CBZ and CBZE were evaluated by HPLC. Induction ratios of CYP2B and CYP3A were evaluated by Western blotting. Serum levels of CBZ and CBZE became maximal after 14 and 7 d, respectively, after CBZ treatment. Both levels gradually, then significantly decreased after 42 d CBZ compared with maximal levels. The induction ratio of CYP2B did not differ between 3, 7, 14, 28 and 42 d CBZ treatment. The induction ratio of CYP3A reached a maximum after 14 d CBZ, then significantly decreased after 28 and 42 d CBZ compared to the maximal rate. The difference between CYP2B and CYP3A induction by CBZ chronic treatment is a novel finding.