Metformin addition attenuates olanzapine-induced weight gain in drug-naive first-episode schizophrenia patients: A double-blind, placebo-controlled study
ABSTRACT The purpose of this study was to assess the efficacy of metformin in preventing olanzapine-induced weight gain.
Forty patients with schizophrenia were randomly assigned to treatment for 12 weeks with olanzapine, 15 mg/day, plus metformin, 750 mg/day (N=20), or olanzapine, 15 mg/day, plus placebo (N=20). This investigation was conducted in a double-blind fashion. Planned assessments included body weight, body mass index, proportion of patients who gained more than 7% of their baseline weight at the end of the 12-week treatment, waist circumference, waist-to-hip ratio, fasting glucose and insulin, insulin resistance index, and scores on the Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS).
Of the 40 patients who were randomly assigned, 37 (92.5%) completed treatments. The weight, body mass index, waist circumference, and waist-to-hip ratio levels increased less in the olanzapine plus metformin group relative to the olanzapine plus placebo group during the 12-week follow-up period. The insulin and insulin resistance index values of the olanzapine plus placebo group increased significantly at weeks 8 and 12. In contrast, the insulin and insulin resistance index levels of the olanzapine plus metformin group remained unchanged. Significantly fewer patients in the olanzapine plus metformin group relative to patients in the olanzapine plus placebo group increased their baseline weight by more than 7%, which was the cutoff for clinically meaningful weight gain. There was a significant decrease in SAPS and SANS scores within each group from baseline to week 12, with no between-group differences. Metformin was tolerated well by all patients.
Metformin was effective and safe in attenuating olanzapine-induced weight gain and insulin resistance in drug-naive first-episode schizophrenia patients. Patients displayed good adherence to this type of preventive intervention.
- SourceAvailable from: Roberto Coccurello[Show abstract] [Hide abstract]
ABSTRACT: Beside the therapeutic improvement over first-generation antipsychotics, the fact that prescription of atypical agents is also associated to the emergence of severe metabolic derangement in patients is not a mystery anymore. Body weight gain, dyslipidemia, adiposity, impaired glucose homeostasis, insulin and leptin resistance and new-onset type II diabetes are all part of a syndromic cluster of vast medical concern. Thus, clinical reports and rodent models of atypical antipsychotic-associated metabolic impairment have growth in parallel as separate territories. This review focuses on the attempt to take a snapshot of the present developing moment and to describe to what extent clinical data are reflected by the findings derived from animal studies. This aim is pursued through different steps that, starting from the criteria necessary to characterize the "atypicality" of atypical drugs, then explore the consistency among clinical and animal-based data. The endpoint of this survey consists in the analysis of the potential mechanisms underlying the metabolic derangement induced by this class of drugs. It is, indeed, our opinion that some atypical antipsychotics should be viewed as potent obesogenic factors that can be exploited as valuable tools to shed light into the elusive dilemma of obesity. For this reason, recently identified obesogenic and diabetogenic mechanisms are the background on which the present work is built and some novel forthcoming lines of investigation suggested.Pharmacology [?] Therapeutics 09/2010; 127(3):210-51. DOI:10.1016/j.pharmthera.2010.04.008 · 7.75 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Weight gain is a clinically important side effect of antipsychotic drug therapy. The aim of this study was to determine the effect of the antidiabetic drug metformin on antipsychotic-induced weight gain in non-diabetic patients. In a systematic literature review we identified 195 citations from which seven randomized, placebo-controlled studies (398 patients) were included in the final analysis. Studies in adults (n ¼5) and in children (n ¼2) were analysed separately. Compared with placebo, metformin treatment caused a significant body weight reduction in adult non-diabetic patients treated with atypical antipsychotics (4.8%, 95% CI 1.6 to 8.0) and in children (4.1%, 95% CI 2.2 to 6.0). There was evidence of substantial heterogeneity among studies, and when the analysis was restricted to patients with a manifest (>10%) body weight increase prior to randomisation metformin reduced weight by 7.5% (95% CI 2.9 to 12.0). The effect was larger in Asians (7.8%, 95% CI 4.4 to 11.2) than in Hispanics (2.0%, 95% CI 0.7 to 3.3). In conclusion, metformin has a pronounced weight-reducing effect in antipsychotic-treated patients, especially in those with a manifest weight gain. Although direct comparisons are lacking, the observed effect on body weight compares favourably with the effect of sibutramine and orlistat, approved for weight reduction. However, metformin is not approved for use in non-diabetic patients and it is still not generally advisable to recommend metformin to counteract antipsychotic-induced weight gain.
- [Show abstract] [Hide abstract]
ABSTRACT: Schizophrenia in subjects younger than 13 years is defined as very-early-onset schizophrenia, and its prevalence is estimated at 1 in 10000, while early-onset schizophrenia occurs between 13 and 17 years, and its prevalence is about 0.5%. Only a minority of youths show a complete recovery, and the majority of patients present a moderate to severe impairment at the outset. Treatment of schizophrenia always needs both pharmacological and nonpharmacological interventions. Nonpharmacological interventions include counselling for the patients and the family, psychological support, behavioural treatments, social and cognitive rehabilitation, assistance in social and scholastic activities, enhancement of social skills and family support. Pharmacological treatment is necessary for remission and control of positive and negative symptoms. Furthermore, proper pharmacotherapy can greatly increase the efficacy of psychosocial interventions. Available literature on pharmacotherapy in children and adolescents with schizophrenia is critically reviewed, including both first-and second-generation antipsychotics. Data on efficacy and safety are reported for all the marketed atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine, ziprasidone and aripiprazole), based on randomized, placebo-controlled studies and the most relevant open-label or naturalistic studies. Adverse effects of concern are closely analysed, such as extrapyramidal side effects and tardive dyskinesia, metabolic syndrome (including hyperglycaemia and hyperlipidaemia), weight gain, hyperprolactinaemia, hepatotoxicity, seizures, and cardiovascular and haematological adverse effects. Finally, practical guidelines for the management of specific clinical situations are provided: the first phases and the long-term approach to pharmacotherapy, the treatment refractoriness and the use of clozapine in youths, the agitated adolescent and the treatment of negative symptoms and of affective co-morbidity. Current experience indicates that, based on low rates of remission, low effect size of medications and frequent adverse effects, mainly metabolic syndrome, further research is warranted, with both randomized, placebo-controlled studies and long-term, naturalistic follow-up of large samples of patients with different age ranges.Drugs 01/2011; 71(2). · 4.13 Impact Factor