The effect of naltrexone on body fat mass in olanzapine-treated schizophrenic or schizoaffective patients: A randomized double-blind placebo-controlled pilot study

Abstract

Olanzapine (OLZ), a commonly prescribed second generation antipsychotic drug, is associated with obesity and metabolic syndrome and may contribute to increased cardiovascular morbidity and mortality. Opioidergic neurotransmission may be implicated in the development of these metabolic disturbances. The objective of this study was to assess the effects of opioid blockade on OLZ-treated patients' metabolic status. Patients with schizophrenia or schizoaffective disorder (n=30) on a stable dose of OLZ were randomized in a double-blind fashion to receive an opioid receptor antagonist, naltrexone (NTX), (n=14) or placebo (n=16). The primary outcome measure was the change in body mass index (BMI) at 12 weeks. Secondary measures included body fat and fat-free mass, along with homeostasis model assessment-estimated insulin resistance (HOMA-IR), plasma lipids and liver function tests (LFTs). There was no significant change in BMI between the treatment arms. However, in comparison to the OLZ + placebo combination, the OLZ + NTX group displayed a significant decrease in the fat and increase in fat-free mass along with a trend towards improvement in HOMA-IR values. There were no significant differences in plasma lipids and LFTs. These findings suggest that addition of NTX to OLZ may attenuate OLZ-induced body fat mass gain. A larger study of longer duration will be needed to confirm these results.

Oral glucose tolerance test performance in olanzapine-treated schizophrenia-spectrum patients is predicted by BMI and triglycerides but not olanzapine dose or duration

“…Participants' characteristics are detailed in Table , including mean daily dose and duration of olanzapine. Further participants' selection methodology and clinical trial data of some of these participants are reported elsewhere (Taveira et al, ).…”

An Overview of Links Between Obesity and Mental Health

“…Antagonism at this serotonin receptor increases appetite, which might explain the antipsychotic treatmentinduced weight gain [78]. Second-generation antipsychotics have also been hypothesized to induce weight gain by different mechanisms: (1) contributing to decreased energy expenditure; (2) enhancing the opioidergic activity which could further deteriorate the preexisting hedonic alterations in schizophrenia patients [79]; (3) altering the function of lateral hypothalamic serotonin and/or histamine medidated actions [80]; (4) inducing dopamine antagonists; (5) altering glucose uptake by blocking glucose accumulation directly at the level of the glucose transporter (GLUT) protein in cells derived from both peripheral and brain tissue [81]; (6) inducing insulin resistance and impairments in insulin secretion directly [82,83], and (7) promoting triglyceride accumulation by stimulating lipogenesis and inhibiting lipolysis [74]. Second-generation antipsychotics also target the deregulated HPA axis.…”

A Randomized, Double-Blind, Placebo-Controlled Pilot Study of Naltrexone to Counteract Antipsychotic-Associated Weight Gain

“…While it is not possible to exclude other mechanisms of weight loss with naltrexone, it is helpful to note that naltrexone alone does not produce appreciable weight loss in obese/overweight individuals who are not on antipsychotic medications [43] . Also it is interesting to note that the partially negative study by Taveira et al recruited only subjects on olanzapine, an antipsychotic with relatively low D2 and very strong H1 blockade [32] . This may indirectly support the working hypothesis of this paper, that naltrexone might counteract the D2 blockade-related portion of antipsychotic induced weight gain.…”

“…This may indirectly support the working hypothesis of this paper, that naltrexone might counteract the D2 blockade-related portion of antipsychotic induced weight gain. On the other hand, Taviera et al showed a decrease in fat mass, and since both groups lost weight, presumably due to nutritional counseling provided, it might be hard to discern differences in naltrexone and placebo groups [32] . Clearly studies with larger sample sizes are necessary.…”

“…Opioid receptor blockers, such as naltrexone, have been studied as weight loss agents and have not been shown to be consistently effective by themselves; however, they may be able to counteract the part of antipsychotic-induced weight gain that might be caused by D2 blockade. A recent study of add-on naltrexone treatment for subjects using olanzapine reported no significant change in weight, however a decrease of fat mass was reported [32] .…”