Effect of topiramate on plasma concentrations of clozapine, olanzapine, risperidone, and quetiapine in patients with psychotic disorders.

OBJECTIVES: To investigate the effect of topiramate on the steady-state plasma concentrations of the second-generation antipsychotics--clozapine, olanzapine, risperidone, and quetiapine--in patients with schizophrenia or bipolar disorder. METHODS: Thirty-eight outpatients on long-term treatment with clozapine (250-500 mg/d, n = 10), olanzapine (10-20 mg/d, n = 12), risperidone (3-6 mg/d, n = 9), or quetiapine (200-600 mg/d, n = 7) received adjunctive topiramate, gradually titrated up to a final dosage of 200 mg/d for 6 weeks. Pharmacokinetic assessments were made at baseline and at the end of treatment weeks 4 and 8 at topiramate dosages of 100 and 200 mg/d, respectively. RESULTS: Plasma concentrations of clozapine and its metabolite (norclozapine), olanzapine, risperidone and its metabolite (9-hydroxy-risperidone), and quetiapine were not significantly modified during concomitant administration of topiramate. Adjunctive topiramate therapy was well tolerated in all groups. CONCLUSIONS: These findings indicate that topiramate, at the dosages recommended for use as a mood stabilizer, does not affect the plasma levels of the new antipsychotics-clozapine, olanzapine, risperidone, and quetiapine.

Low-Dose of Bergamot-Derived Polyphenolic Fraction (BPF) Did Not Improve Metabolic Parameters in Second Generation Antipsychotics-Treated Patients: Results from a 60-days Open-Label Study.

Objectives: The nutraceutical approach to the management of metabolic syndrome (MetS) might be a promising strategy in the prevention of cardio-metabolic risk. Low-dose bergamot-derived polyphenolic fraction (BPF) has been proven effective in patients with MetS, as demonstrated by a concomitant improvement in lipemic and glycemic profiles. The present study was aimed to further explore, in a sample of subjects receiving second generation antipsychotics (SGAs), the effects on body weight and metabolic parameters of a low dose of BPF (500 mg/day) administered for 60 days. Methods: Twenty-eight outpatients treated with SGAs assumed BPF at single daily dose of 500 mg/day for 60 days. Body weight, BMI, fasting levels of glucose, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides were determined; moreover, Brief Psychiatric Rating Scale (BPRS) was administered. Results: Low-dose BPF administration did not change clinical and metabolic parameters, as well as clinical symptoms in the study sample. At the end of the trial, among completers (n = 24) only nine patients (37.5%) reached an LDL reduction >0 but <50%. Conclusions: Our results demonstrate that patients treated with SGAs may need higher BPF doses for obtaining the positive effects on body weight and metabolic parameters previously found in the general population at lower doses.

Plasma concentrations of risperidone and olanzapine during coadministration with oxcarbazepine.

PURPOSE: Oxcarbazepine (OZC) is a second-generation antiepileptic drug (AED) that also may be used as a mood stabilizer. Unlike carbamazepine (CBZ), which is an inducer of the cytochrome P-450 isoforms and may accelerate the elimination of several therapeutic agents, OXC seems to have only a modest inducing action. The aim of this investigation was to evaluate the effect of a treatment with OXC on plasma concentrations of the new antipsychotics risperidone and olanzapine. METHODS: OXC, at a dosage of 900-1,200 mg/day, was administered for 5 consecutive weeks to 25 outpatients, 10 men and 15 women, aged 25 to 64 years, with bipolar or schizoaffective disorder. Twelve patients were stabilized on risperidone therapy (2-6 mg/day) and 13 on olanzapine (5-20 mg/day). Steady-state plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) and olanzapine were measured by high-pressure liquid chromatography (HPLC) before addition of OXC and after 5 weeks from the start of adjunctive treatment. RESULTS: OXC caused only minimal and no significant changes in the mean plasma levels of risperidone (from 5.6 +/- 3.6 ng/ml at baseline to 4.8 +/- 2.6 ng/ml at week 5), 9-OH-risperidone (from 23.6 +/- 7.5 to 24.7 +/- 7.4 ng/ml), and olanzapine (from 26.5 +/- 5.7 ng/ml at baseline to 27.8 +/- 5.1 ng/ml). OXC coadministration with either risperidone or olanzapine was well tolerated. CONCLUSIONS: Our findings indicate that OXC does not affect the elimination of risperidone and olanzapine, thus confirming its weak inducing effect on hepatic drug-metabolizing enzymes.