Moderators and mediators of antipsychotic response in delusional disorder: Further steps are needed.

Delusional disorder (DD) has been traditionally considered a relatively rare and treatment-resistant psychotic disorder. In the last decade, increasing attention has focused on therapeutic outcomes of individuals affected by this disorder. The aim of this paper is to provide a synthesis of the literature addressing two very important questions arising from DD research: (1) For which patients with DD do antipsychotic medications work best (the moderators of response); and (2) What variables best explain the relationship between such treatments and their effectiveness (the mediators of response). We searched PubMed and Google Scholar databases for English, German, French and Spanish language papers published since 2000. We also included a few classic earlier papers addressing this topic. Variables potentially moderating antipsychotic response in DD are gender, reproductive status, age, duration of illness, the presence of comorbidity (especially psychiatric comorbidity) and its treatment, brain structure, and genetics of neurochemical receptors and drug metabolizing enzymes. Antipsychotic and hormonal blood levels during treatment, as well as functional brain changes, are potential mediating variables. Some, but not all, patients with DD benefit from antipsychotic treatment. Understanding the circumstances under which treatment works best can serve to guide optimal management.