Aripiprazole Added to Overweight and Obese Olanzapine-Treated Schizophrenia Patients

Abstract

Olanzapine treatment has been associated with clinically meaningful weight increases, hypertriglyceridemia, insulin resistance and diabetes mellitus. There are few options for olanzapine-responders who fail other antipsychotic agents. Aripiprazole is a potent (high-affinity) partial agonist at D2 and 5-HT1A receptors and a potent antagonist at 5-HT2A receptor and is associated with less weight gain than olanzapine. We report the results of a 10-week placebo controlled, double-blind crossover study that examined 15 mg/day aripiprazole's effects upon weight, lipids, glucose metabolism, and psychopathology in overweight and obese schizophrenia and schizoaffective disorder subjects treated with a stable dose of olanzapine. During the 4 weeks of aripiprazole treatment there were significant decreases in weight (p = .003) and BMI (p = .004) compared to placebo. Total serum cholesterol (p = .208), HDL-cholesterol (p = .99), HDL-2 (p=.08), HDL-3 (p=.495) and LDL- cholesterol (p=.665) did not change significantly comparing aripiprazole treatment to placebo treatment. However, total serum triglycerides (p = .001), total VLDL-cholesterol (p=.01), VLDL 1- &2-cholesterol (p=.012) decreased significantly during the aripiprazole treatment phase. VLDL-3-cholesterol tended lower during aripiprazole, but the decrease was not significant (p=.062). There was a decrease in c-reactive protein comparing aripiprazole treatment to placebo though it did not reach significance (p=.087). The addition of aripiprazole to a stable dose of olanzapine was well tolerated and resulted in significant improvements on several outcome measures that predict risk for medical morbidity.

Effects of chronic oral treatment with aripiprazole on the expression of NMDA receptor subunits and binding sites in rat brain

“…The low (10 mg/kg/day) and high (40 mg/kg/day) doses lie in the range of other animal trials with subcutaneaous (Li et al 2005), oral (Inoue et al 1998;Kalinichev et al 2005) (Dr. Kikutichi, personal communication), or intraperitoneal (Cheng et al 2008;Semba et al 1995;Semba et al 1996) routes of application. APZ treatment showed a tendency to induce weight loss in our system (Segnitz et al 2009) in contrast to the animal study of Kalinichev et al (2005) but quite in concert with clinical observations (Englisch et al 2009;Henderson et al 2009). The low expression levels of NR2C and NR2D in frontocortical regions have been reported previously (Goebel and Poosch 1999).…”

BAP guidelines on the management of weight gain, metabolic disturbances and cardiovascular risk associated with psychosis and antipsychotic drug treatment

“…The same group then reported the results of a 10-week placebo controlled, double-blind crossover study comparing the effects of 15 mg/day of aripiprazole versus placebo on weight, lipids and glucose metabolism in overweight and obese people with schizophrenia treated with a stable dose of olanzapine (Henderson et al, 2009). Participants received either aripiprazole for 4 weeks, followed by a 2-week treatment adjuvant washout and then placebo for 4 weeks or the reverse of this.…”

Factors associated with non evidence-based prescribing of antipsychotics

“…These include cross titration of antipsychotics during switching [Taylor, 1997], clozapine augmentation to improve efficacy [Taylor and Smith, 2009], managing side effects (e.g. adding aripiprazole to combat raised prolactin or metabolic symptoms [Shim et al 2007;Henderson et al 2009]) and rapid tranquillisation .…”