Second-generation antipsychotics (SGAs) for treating schizophrenia were developed to address the safety and efficacy issues associated with first-generation antipsychotics (FGAs).

Today, three-quarters of adult patients prescribed antipsychotic medications take SGAs, accounting for 93 percent of the $2.8 billion spent each year on these medications. But recent published articles have questioned whether there are clinically important differences in patient outcomes between FGAs and SGAs.

Researchers at the Agency for Healthcare Research and Quality (AHRQ) reviewed 114 studies involving 22 comparisons of FGAs and SGAs. The researchers assessed differences in symptoms, adverse events such as diabetes, mortality, tardive dyskinesia (neurological disorder that causes involuntary, repetitive movements, a common side effect of long-term antipsychotic use), and major metabolic syndrome in patients aged 18-24 with schizophrenia and related psychosis. The researchers found little research to support the use of SGAs for treating positive symptoms.

They found moderate evidence that the SGAs olanzapine and risperidone treated negative symptoms more effectively than the FGA haloperidol based on the Scale for the Assessment of Negative Symptoms (SANS). There was insufficient evidence to compare adverse events.

The researchers recommend more focused studies on drug safety. They conclude that the current evidence is inadequate to inform clinical decisions.