Newer oral atypical antipsychotic agents: a review.

“black-box” warnings for all antipsychotic drugs.2 Antipsychotic agents may be classified in several ways. Commonly, they can be designated as older drugs (often called conventional or “typical” antipsychotics) and newer “atypicals.” The term atypical refers to the perceived lower likelihood of extrapyramidal symptoms, a sequela that had been deemed characteristic of the first generation of antipsychotic drugs. The atypicals are widely prescribed based on the perception that they are more effective and produce fewer side effects than the typicals, even though some atypicals are much more expensive. CATIE (Clinical Antipsychotic Trials in Intervention Effectiveness), a large study published in 2005, cast doubt on the relative overall effectiveness of the atypicals, which seemed to perform no better than perphenazine (formerly Trilafon, Schering-Plough), an older, less expensive typical antipsychotic medication.3 Some observers have suggested a return to the use of the less expensive typical medications. In this setting, the field is in need of better agents to bring about improved antipsychotic effects, a lower rate of refractory illness, and reduced both metabolic and neuro logical side effects. The atypical antipsychotics include risperidone (Risperdal, Janssen), olanzapine (Zyprexa, Eli Lilly), quetiapine (Seroquel, AstraZeneca), ziprasidone (Geodon, Pfizer), and ari piprazole (Abilify, Bristol-Myers Squibb/Otsuka). Clozapine (Clozaril, Novartis) is usually included in this list as the prototypical agent, although its potential for bone marrow suppression sets it apart. Since the introduction of aripiprazole in 2002, there has been a relative hiatus in the development of new atypical antipsychotic drugs. In this article, we review four oral atypical antipsychotic agents introduced since 2007: paliperidone (Invega, Ortho-McNeil-Janssen), iloperidone (Fanapt, Vanda), asenapine (Saphris, Organon), and lurasidone (Latuda, Sunovion). We discuss their classification, indications, mechanism of action, clinical trials, efficacy, adverse effects, comparisons with other antipsychotics, new indications being sought, dosing and administration, absorption, distribution, metabolism, excretion, contraindications, FDA warnings, and drug–drug interactions. We excluded antipsychotic agents that are currently under investigation and those that have not yet been approved by the FDA. We conducted a Medline search for the terms paliperidone, iloperidone, asenapine, and lurasidone to identify efficacy and tolerability trials for each drug. Product information and results from unpublished studies were obtained from the manu facturers. After completing this program, readers should be able to: