Olanzapine is an atypical antipsychotic that is useful in schizophrenia and bipolar affective disorder, but its use is associated with troublesome weight gain and metabolic syndrome. A variety of pharmacological agents has been studied in the efforts to reverse weight gain induced by olanzapine, but current evidence is insufficient to support any particular pharmacological approach. We conducted a systematic review and meta-analysis of randomized controlled trials of metformin for the treatment of olanzapine-induced weight gain.
Systematic review of the literature revealed 12 studies that had assessed metformin for antipsychotic-induced weight gain. Meta-analysis was performed to see the effect size of the treatment on body weight, waist circumference and body-mass index BMI. Weighted mean difference WMD for body weight was 5. Therefore, zyprexa and weight gain, a random effects model was used to calculate WMD, which was 1. Existing data suggest that short term modest weight loss is possible with metformin in patients with olanzapine-induced weight gain.
Body weight gain and metabolic alterations are clinically relevant side effects of atypical antipsychotics which are evident after approximately 10 weeks of treatment [ 1 ].
Olanzapine is linked to clinically significant body weight gain ranging from 0. Weight gain with olanzapine has been found to be significantly higher than with other atypical antipsychotics, except for clozapine [ 4 ]. It is hypothesized that appetite stimulation and insulin resistance are the underlying mechanisms for olanzapine-induced weight gain [ 56 ].
A possible cause of appetite stimulation has been suggested to involve serotonin 5-HT 2C and histamine H 1 -receptor antagonism, resulting in food craving and binge eating [ 7 ]. Therefore, effective pharmacological and nonpharmacological strategies are urgently required for optimal body weight control during olanzapine treatment [ 8 ].
Various medications such as amantadine, nizatidine, ranitidine, famotidine, topiramate, fenfluramine, reboxetine, fluoxetine, fluvoxamine, sibutramine, dextroamphetamine, d-fenfluramine, orlistat, phenylpropanolamine, rosiglitazone and metformin have been reported to counteract effectively antipsychotic-induced body weight gain [ 9 — 11 ].
The antidiabetic agent metformin, zyprexa and weight gain, a biguanide, is particularly attractive because of its dual mechanism of decreasing body weight gain and improving insulin sensitivity, zyprexa and weight gain, both of which are affected by olanzapine.
Metformin has been demonstrated to improve glycaemic control and promotes a moderate weight loss in both diabetic and non-diabetic subjects [ 1213 ]. Studies that have assessed metformin for olanzapine-induced weight gain report weight loss, though the effect varies across studies. In the systematic review by Bushe et al. They were not able to combine studies for meta-analysis zyprexa and weight gain to the high level of heterogeneity.
Further, they noted that the effect of dietary and lifestyle interventions could not be teased out. In another recent systematic review and meta-analysis [ 15 ], metformin treatment caused a significant body weight reduction in adult non-diabetic patients treated with atypical antipsychotics 4. As the weight gain pattern is different for olanzapine as compared with other atypical antipsychotics and it is one of the most commonly used antipsychotics, we conducted a systematic review and meta-analysis with an objective to determine the effects of metformin for reducing or preventing weight gain associated with olanzapine.
We inspected the zyprexa and weight gain list of all identified studies, including existing reviews for relevant citations. The search was restricted to publications in the English language. One reviewer SKP initially evaluated the abstracts from the literature search. The following criteria were used to identify the studies:. Two reviewers SKP and NG decided, independently, whether individual studies met the inclusion zyprexa and weight gain. Disagreements were resolved by discussion with anti depressants drowsiness third reviewer AKJ.
We used a standardized zyprexa and weight gain, and extracted data which included patient and study characteristics, outcome measures and study results. The methodological quality of included trials in this review was done using the Jadad Scale [ 17 ]. Vitamin k and antibiotic therapy includes three items: Scoring was done as follows: Cut-off of two points on the Jadad scale was considered.
Meta-analyses were undertaken to estimate overall treatment effects where the trials were considered to be similar enough to combine using Rev Man 4. This decision was based on assessing similarity of trial characteristics as well as results.
Separate meta-analyses were undertaken for each outcome body weight, waist circumference and BMI. Otherwise, a fixed-effect model was used for analysis, zyprexa and weight gain.
The combined search strategies identified 12 papers on use of metformin in olanzapine-induced weight gain. Three studies were excluded because of the following reasons: Four other papers were commentaries on other studies, whereas Morrison et al. Finally, four studies met the review inclusion criteria total subjects and were included in the final analysis [ 24 — 27 ].
Characteristics of included studies are summarized in Table 1. One of the included studies [ 25 ] had results from four groups metformin only, metformin and lifestyle intervention, lifestyle intervention only or placeboof which only comparison between metformin and placebo was included and the other two zyprexa and weight gain were excluded in our meta-analysis.
In the study of Baptista et al. All of the four studies were described as randomized. Concealment of allocation was adequately reported in two studies [ 2425 ]. All the studies were double-blind. The dropout rate ranged from 7. Forest plots for meta-analyses for body weight gain, waist circumference and BMI are presented in Figures 1 — 3.
Weighted mean difference for body weight was 5. Forest Plot showing body weight kg at 12 weeks in randomized controlled trials comparing metformin and placebo for olanzapine-induced weight gain.
Forest plot showing waist circumference cm at 12 weeks in randomized controlled trials comparing metformin and placebo for olanzapine-induced weight gain. In our meta-analysis, weight reduction was 5, zyprexa and weight gain. The adverse events reported with metformin were similar to placebo groups. These results encourage additional studies in more homogenous populations on the potential use of metformin in assisting olanzapine-treated patients in the long-term control of body weight and BMI.
Baseline screening and a monitoring plan must zyprexa and weight gain initiated on commencement of antipsychotic treatment [ 29 ]. With significant weight gain or emerging metabolic effects, the risks and benefits of antipsychotic choice and concomitant medications should be re-evaluated. Although metformin may not be routinely indicated for all patients on olanzapine as prophylaxis based on the current evidence, its use is justified in patients having olanzapine-induced weight gain with no contraindication to metformin.
Our study is limited by the number of studies included for meta-analysis, zyprexa and weight gain. The small number of studies did not allow us to conduct tests for publication bias.
Also, sensitivity analysis was not performed in our study. Nevertheless, heterogeneity was not seen for body weight gain and BMI in the studies. For waist circumference, a random effects model was used to curb the problem of heterogeneity. Although, statistically homogenous, there were differences in zyprexa and weight gain study population in four studies. Weight loss in the Wu et al. Furthermore, two of the studies [ 2426 ] have evaluated prevention of olanzapine-induced weight gain, whereas the other two [ 2527 zyprexa and weight gain have studied reversal of weight gain.
Although these studies were combined in our review, it has been suggested that metformin appears to benefit more when started early in the course of treatment [ 30 ]. Nevertheless, the mechanism of action of metformin does not seem to vary in both these situations, which justifies the combination of these studies in our meta-analysis.
We suggest that all future studies should respect standards of measuring outcomes and of reporting data in order to enhance the comparability of study results. National Center for Biotechnology InformationU. Br J Clin Pharmacol. Received May 30; Accepted Aug 6.
This article has been cited by other articles in PMC. Abstract Olanzapine is an atypical antipsychotic that is useful in schizophrenia and bipolar affective disorder, but its use is associated with troublesome weight gain and metabolic syndrome. Metformin, an anti-hyperglycaemic agent, has been used to treat or prevent weight gain associated with olanzapine.
Meta-analyses on studies that have examined the use of metformin for treatment of antipsychotic-induced weight gain report significant heterogeneity, zyprexa and weight gain. Introduction Body weight gain and metabolic alterations are clinically relevant side effects zyprexa and weight gain atypical antipsychotics which are evident after approximately 10 weeks of treatment [ 1 ].
The following criteria were used to identify the studies: Randomized, double-blind clinical trials comparing metformin with placebo for olanzapine-induced weight gain. Data extraction Two reviewers SKP and NG decided, independently, whether individual studies met the inclusion criteria. Assessment of methodological quality of studies The methodological quality of included trials in this review was done using the Jadad Zyprexa and weight gain [ 17 ].
Quantitative data synthesis Meta-analyses were undertaken to estimate overall treatment effects where the trials were considered to be similar enough to combine using Rev Man 4. Results Studies included The combined search strategies identified 12 papers on use of metformin in olanzapine-induced weight gain. Table 1 Characteristics of included studies. Olanzapine 5—20 mg plus metformin to mg daily. Open in a separate window. Study quality All of the four studies were described as randomized.
Meta-analysis Forest plots for meta-analyses for body weight gain, waist circumference and BMI are presented in Figures 1 — 3. Discussion Existing data suggest that short term modest weight loss is possible with metformin in patients zyprexa and weight gain olanzapine-induced weight gain. Competing interests There are no competing interests to declare.
Sources of funding None. Dosing the antipsychotic medication olanzapine. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.
N Engl J Med. Olanzapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev. Glucose metabolism in patients with schizophrenia treated with atypical antipsychotic agents: Clozapine and olanzapine are associated with food craving and binge eating: