Probiotics Plus Dietary Fiber Supplements Attenuate Olanzapine-Induced Weight Gain in Drug-Naïve First-Episode Schizophrenia Patients: Two Randomized Clinical Trials

Abstract

Background and Hypothesis Antipsychotic-induced weight gain is associated with alterations to the composition of the gut microbiota. The purpose of this study was to determine the effect of probiotics plus dietary fiber on antipsychotic-induced weight gain. Study Design Two sequential, randomized clinical trials were conducted. In Study 1, 90 drug-naïve, first-episode schizophrenia patients were randomized to receive either olanzapine plus probiotics or olanzapine monotherapy for 12 weeks. In Study 2, 60 drug-naïve, first-episode schizophrenia patients were randomly assigned to receive either olanzapine plus probiotics and dietary fiber or olanzapine monotherapy for 12 weeks. Study Results In Study 1, no significant differences in weight gain were observed between the two groups. The insulin resistance index (IRI) was lower in the olanzapine plus probiotics group compared with the olanzapine monotherapy group at week 12 (estimated mean difference, −0.65, [95% confidence interval (CI), −1.10 to −0.20]; p = .005). In Study 2, weight gain was lower in the probiotics plus dietary fiber group than in the olanzapine monotherapy group at week 12 (estimated mean difference −3.45 kg, [95% CI, −5.91 to −1.00]; p = .007). At week 12, IRI increased significantly in the olanzapine monotherapy group (mean, 1.74; standard deviation (SD) = 1.11, p < .001), but not in the olanzapine plus probiotics and dietary fiber group (mean 0.47, SD = 2.16, p = .35) with an estimated mean difference of −0.95 between the two groups [95% CI, −1.77 to −0.14]; p = .022). Conclusions These results provide support for the efficacy and safety of probiotics plus dietary fiber in attenuating antipsychotic-induced weight gain in drug-naïve, first-episode schizophrenia patients.

Gut microbiota serve as a risk predictor of weight gain in schizophrenia patients with antipsychotic medication

“…Lactobacillus is a typical probiotic that has been widely used to enhance intestinal barrier [49], reduce visceral fat mass [50,51], maintain body weight [52], and improve glucose tolerance [53]. Recently, Lactobacillus has also been proved to be effective in curbing antipsychotics-induced weight gain in patients with SZ [17,18]. Thus, these synergistic effects may further support the potential uses of "supplementation with Lactobacillus" in antipsychotic-induced weight gain by increasing the abundance of healthy bacteria.…”

“…Recent studies have found a potential link between gut bacteria and aberrant BMI after antipsychotic medication. Two randomized clinical trials demonstrated that modulating the gut milieu with probiotics and dietary ber could effectively ameliorate antipsychotics-induced weight gain for SZ patients [17,18], suggesting a potential link between microbial dysbiosis and metabolic disorders. Hence, we conducted a cross-sectional study to compare the gut microbiota between SZ-O and SZ-N groups.…”

“…Recently, two randomized clinical trials demonstrated that probiotics plus dietary ber can effectively reduce the antipsychotic-induced weight gain and metabolic disturbance in SZ patients [17,18]. And such favorable effects were linked to an increased abundance of gut microbiota [18].…”

Reviewing the Potential Therapeutic Approaches Targeting the Modulation of Gastrointestinal Microflora in Schizophrenia

“…From this evidence, additional perspectives and interests towards the role of Bifidobacterium, Lactobacillus and Enterococcus (1 × 10 7 CFU each [46]/ ≥ 5.0 × 10 7 CFU/g [47]) in the amelioration of olanzapine-induced body weight arose [46,47]. Yang et al [46] emphasized a between-group difference, after four weeks treatment, in weight (p < 0.05) and body mass index (BMI) (p < 0.05) that lasted for eight to twelve weeks of treatment (p > 0.05) with no differences in terms of appetite during the analyzed period (p > 0.05); a non-statistical significance mean time from olanzapine initiation to appetite changes was also obtained (p = 0.22).…”

“…Yang et al [46] emphasized a between-group difference, after four weeks treatment, in weight (p < 0.05) and body mass index (BMI) (p < 0.05) that lasted for eight to twelve weeks of treatment (p > 0.05) with no differences in terms of appetite during the analyzed period (p > 0.05); a non-statistical significance mean time from olanzapine initiation to appetite changes was also obtained (p = 0.22). Moreover, two randomized controlled trials (RCTs) conducted by Huang et al [47] have been conducted to evaluate the benefits brought by Bifico. In the first twelve-week study, no effects of the probiotics on weight gain (p < 0.005) were observed, whereas in the second study, probiotics and dietary fiber exerted a beneficial impact (p = 0.007) per insulin resistance index (IRI) value (p < 0.005/p < 0.001), particularly in olanzapine monotherapy, but not in olanzapine combined with probiotics and dietary fiber (p = 0.35).…”