Metabolic and Cardiac Side Effects of Second-generation Antipsychotics: What Every Clinician Should Know

Abstract

In 2007, 5 of the 7 second-generation antipsychotics were listed in the Top 200 Drugs prescribed by retail sales in the United States. Cardiovascular disease is the leading cause of natural death in individuals with schizophrenia. Second-generation antipsychotics have been implicated with metabolic and cardiovascular adverse effects, and it is important for nonpsychiatric practitioners to be familiar with the monitoring parameters recommended for these agents. This article discusses the risk of weight gain, hyperglycemia, hyperlipidemia, hyperprolactinemia, and cardiovascular concerns associated with second-generation antipsychotic agents. It also discusses the proposed mechanisms for each of these adverse effects. Furthermore, it reviews suggested monitoring parameters to help manage cardiovascular disease in this patient population, and to improve the gap that exists between mental health care and physical health care in the schizophrenic population.

Structural contributions of antipsychotic drugs to their therapeutic profiles and metabolic side effects

“…2005). Weight gain associated with antipsychotics is largest within the first three months of therapy and continues over 52 weeks of treatment (Breden et al. 2009).…”

“…Long‐term treatment with phenothiazines causes severe effects on dilatation cardiomyopathy (Volkov 2009). Sertindole, ziprasidone, haloperidol, and clozapine administration have been reported to increase the QTc interval in a dose‐dependent manner in patients treated for schizophrenia (Breden et al. 2009; Miceli et al.…”

“…The majority of atypical antipsychotic drugs are associated with severe weight gain, type II diabetes mellitus, hyperglycemia, dyslipidemia, insulin resistance, cardiovascular disease, hyperprolactemia, and hypertension (Allison et al 1999;Jones et al 2001;Wetterling 2001;Gardner et al 2005;Holt 2006;Mathews and Muzina 2007;Han et al 2008;Breden et al 2009;Parsons et al 2009). The risk of weight gain is high with clozapine and olanzapine, moderate with quetiapine and typical antipsychotics, low with risperidone and minimal with aripiprazole, molindone and ziprasidone (Sussman 2003;Gardner et al 2005;Llorente and Urrutia 2006;Mathews and Muzina 2007).…”

“…Phase I of the CATIE study also reported the following ratios of patients gaining significant weight after long term antipsychotic treatment: 30% with olanzapine, 16% with quetiapine, 14% with risperidone, and 7% with ziprasidone (Lieberman et al 2005). Weight gain associated with antipsychotics is largest within the first three months of therapy and continues over 52 weeks of treatment (Breden et al 2009). Furthermore, post-synaptic changes can also occur with different doses and durations of antipsychotic treatment.…”

In Vivo Pharmacological Evaluations of Novel Olanzapine Analogues in Rats: A Potential New Avenue for the Treatment of Schizophrenia

“…Olanzapine (Olz) is an effective atypical antipsychotic drug used for treating severe psychiatric disorders, including schizophrenia and bipolar disorder [1] , [2] . However, Olz administration is associated with excessive weight gain and severe metabolic side effects such as type II diabetes mellitus, hyperglycemia, dyslipidemia, and insulin resistance [1] , [3] , [4] , [5] , [6] . A novel antipsychotic drug that retains the clinical efficacy of Olz but causes less treatment-emergent weight gain would be an invaluable breakthrough in schizophrenia therapy.…”