First- and Second-Generation Antipsychotics Compared in Federal Agency Monograph

This past summer marked the launch of the Agency for Healthcare Research and Quality’s (AHRQ) continuing medical education (CME) monograph “First-Generation Versus Second-Generation Antipsychotics in Adults: Comparative Effectiveness,” intended for psychiatrists as well as general physicians and mental health professionals.

“This monograph presents a succinct summary of the benefits and risks of the use of both first- and second-generation agents in an unbiased fashion,” Mark Rapaport, M.D., chief of psychiatric services at Emory University School of Medicine and a member of APA’s Council on Medical Education and Lifelong Learning, told Psychiatric News. “This is extremely important for clinicians to understand.”

Information included in the monograph is based upon a 2012 systematic review that was undertaken by AHRQ in response to a request from the public about FDA-approved antipsychotics to treat schizophrenia and bipolar disorder in adults.

The study analyzed data from 114 clinical studies of schizophrenia and 12 studies of bipolar disorder in which a first-generation antipsychotic (FGA) or a second-generation antipsychotic (SGA) was used. The study compared the effectiveness, benefits, and adverse effects of the two drug classes. Studies in which antipsychotics were used for the treatment of dementia, an off-label indication, were excluded.

The results, featured in the monograph, showed few clinically significant differences between FGAs (predominately serotonin-dopamine antagonists) and SGAs (dopamine partial agonists) in treating either disease state. Only olanzapine, an SGA, demonstrated a clinically significant advantage over haloperidol, an FGA, in improving negative symptoms, scores on multiple rating scales, and general psychopathology of schizophrenia. For bipolar disorder, no drug class was superior to the other in terms of reducing manic and depressive symptoms.

With regard to adverse events, extrapyramidal symptoms were significantly more likely to be reported for FGAs—especially for haloperidol—than SGAs. The researchers could not draw conclusions regarding which class was more frequently associated with adverse metabolic health consequences, a common side effect of SGAs, due to insufficient studies in which the two classes were compared.

AHRQ noted that because differences between antipsychotic drugs may be clinically meaningful to patients on an individual basis, providers should make patients aware that “not every person responds in the same way to each medicine, and thus it may require trying several medicines before finding the most effective one.” The agency recommends that clinicians discuss these issues with patients before prescribing antipsychotics. ■

To participate in the “First-Generation Versus Second-Generation Antipsychotic in Adults: Comparative Effectiveness” learning activity, click here. Participants can earn a maximum of 1 AMA PRA Category 1 Credit.