16 Despite the initial optimism that SGAs would greatly reduce EPS burden, most SGAs still demonstrate a clinically relevant tendency to induce these symptoms.23,24 In a large-scale effectiveness trial in chronic SCZ patients, SGAs were indistinguishable from a low-dose FGA (perphenazine) in rates of new onset of akathisia and EPS (5% to 10% each, Inhibitors,research,lifescience,medical irrespective

of drug assignment).25 However, meta-analytic reviews of the literature demonstrate that overall EPS burden may be reduced by 30% to 50% with SGAs.26 Because the mechanism of action for all currently approved antipsychotic medications remains blockade of dopamine receptors,27 motor and other side effects (eg, prolactin elevation) remain a concern in the Inhibitors,research,lifescience,medical treatment of SCZ. While SGAs have moderately reduced EPS and substantially reduced TD liability relative to FGAs, these newer antipsychotics are most notable for

their propensity to induce weight gain,28 as well as related metabolic disturbances such as hypertriglyceridemia and hyperglycemia.29 Clozapine and olanzapine are the APDs most frequently- associated with weight gain, but all Inhibitors,research,lifescience,medical APDs, even first-generation agents, seem to share these effects as a group to varying degrees.30 For example,

a largescale effectiveness trial in antipsychotic naïve patients demonstrated clinically significant weight gain (≥7% of baseline) in more than half of patients Inhibitors,research,lifescience,medical treated with haloperidol.9 Obesity has serious implications for overall health and survival due to an increased risk for cardiovascular and malignant disorders31; Inhibitors,research,lifescience,medical these risks may be of particular importance in patients with SZ who often have limited access to health care and decreased motivation for weight reduction secondary to negative symptomatology.13 Unfortunately, Ixazomib molecular weight APD-induced weight gain is very difficult to reverse, even with sophisticated behavioral, dietary, and pharmacological interventions.32 Pharmacogenetic studies of antipsychotic-induced side effects While the side effect profile of APDs is extremely burdensome in the aggregate, there is substantial interindividual variation in the degree of any particular motor or metabolic effect for a given patient.15 Despite extensive STI571 molecular weight research over the last two decades, data on clinical or biological predictors of antipsychotic side effects are limited.