Early clinical trials had suggested a better safety profile for the second-generation antipsychotics (SGAs; e.g. risperidone, olanzapine, quetiapine, aripiprazole) compared to the older first-generation agents (FGAs; e.g. haloperidol and phenothiazines); however, new long-term studies have determined that important adverse events are associated with the use of the SGAs and that their safety profiles differ significantly. This article reviews the most recent publications (September 2007 to September 2011) of long-term studies of antipsychotic pharmacotherapy with a focus on adverse events and tolerability of second-generation antipsychotic medications. A total of 55 studies were included. Most commonly reported adverse events were weight gain, dyslipidemias, glycemic abnormalities, hyperprolactinemia, movement disorders and cardiovascular events.
It would appear that overweight patients and those with dyslipidemia or risk factors for cardiovascular disease are candidates for agents such as aripiprazole or ziprasidone, which have neutral lipid and weight gain profiles. Patients who are not comfortable with the potential risk of developing hyperprolactinemia should not be prescribed risperidone as first line therapy. Those who have arrhythmias should not be treated with clozapine or ziprasidone. More challenging it is to make a straight recommendation for a first-line treatment in patients at risk of movement disorders. Severe SGA-induced adverse events including death have been reported in elderly patients affected by dementia. Adolescents appear to be more susceptible to SGAs adverse events. Potential risks and benefits should always be considered for each individual patient prior to therapy initiation in order to minimize discontinuation rates and treatment failure.