Metabolic Impact of Switching Antipsychotic Therapy to Aripiprazole After Weight Gain

Abstract

Switching antipsychotic regimen to agents with low weight gain potential has been suggested in patients who gain excessive weight on their antipsychotic therapy. In an open-label pilot study, we evaluated the metabolic and psychiatric efficacy of switching to aripiprazole in 15 (9 men, 6 women) outpatients with schizophrenia who had gained at least 10 kg on their previous antipsychotic regimen. Individuals had evaluation of glucose tolerance, insulin resistance (insulin suppression test), lipid concentrations, and psychiatric status before and after switching to aripiprazole for 4 months. A third of the individuals could not psychiatrically tolerate switching to aripiprazole. In the remaining individuals, psychiatric symptoms significantly improved with decline in Clinical Global Impression Scale (by 26%, P = 0.015) and Positive and Negative Syndrome Scale (by 22%, P = 0.023). Switching to aripiprazole did not alter weight or metabolic outcomes (fasting glucose, insulin resistance, and lipid concentrations) in the patients of whom 73% were insulin resistant and 47% had impaired or diabetic glucose tolerance at baseline. In conclusion, switching to aripiprazole alone does not ameliorate the highly prevalent metabolic abnormalities in the schizophrenia population who have gained weight on other second generation antipsychotic medications.

A 12-week, naturalistic switch study of the efficacy and tolerability of aripiprazole in stable outpatients with schizophrenia or schizoaffective disorder

“…Similar to earlier results, we found that CGI-S and PANSS scores were significantly improved 12 weeks after switching (Casey et al, 2003;Kim et al, 2007). However, overall improvement does not necessarily mean a low rate of symptom worsening.…”

“…Aripiprazole has been associated with minimal or no weight gain (Kane et al, 2002;Kasper et al, 2003) compared with olanzapine and most other atypical antipsychotics (McQuade et al, 2004). Using UKU and IAQ, we observed no significant changes in body weight during the trial, similar to a previously conducted switching study (Kim et al, 2007). Prolactin elevation, a frequent side effect of D 2 -blocking antipsychotics, may induce menstrual irregularities, galactorrhea, or sexual dysfunction (Maguire, 2002).…”

“…Clinicians who are concerned about the possibility of reemergence or worsening of psychotic symptoms may decide not to switch their patients to a different antipsychotics, as switching has been associated with an increased risk of relapse (Gardos, 1974;Tandon et al, 2008). Nevertheless, recent switching studies of aripiprazole focused primarily on clinical improvement or tolerability/safety profiles (Casey et al, 2003;Tandon et al, 2006;Kim et al, 2007;Wolf et al, 2007) rather than on symptom worsening.…”

“…The BETA and EU-BETA studies, as well as other switching studies (Casey et al, 2003;Tandon et al, 2006;Kim et al, 2007;Wolf et al, 2007), have focused mainly on the degree of clinical improvement and tolerability/safety profiles. However, data from these studies should be analyzed to determine whether symptom exacerbation occurred, particularly in clinically stable patients, as clinicians who switch patients from one antipsychotic agent to another are most often concerned about the potential for symptom worsening rather than targeting further improvement.…”

Effects of Antipsychotic Medications on Appetite, Weight, and Insulin Resistance

“…24 Olanzapine and clozapine have been reported to activate hypothalamic AMPK pathway via H 1 receptors to increase food intake and body weight gain. 108 Olanzapine has also been reported to regulate feeding behaviour in rats by modulating histaminergic neurotransmission. 109 The role of the H 1 receptor in APD-induced weight gain has also been supported by findings that co-treatment of betahistine (an H 1 agonist and an H 3 antagonist) can significantly reduce olanzapine-induced weight gain in both schizophrenia patients and animals.…”