Does indication drive use, or does use drive indication?

I this issue of The Journal of Clinical Psychiatry, Fu et al1 report on the results of a study of paliperidone palmitate once-monthly in patients diagnosed with schizoaffective disorder. In this well-designed and well-executed trial, paliperidone monthly was used either as monotherapy or as an adjunct to mood stabilizers or antidepressants. The subjects were randomized to continue paliperidone monthly or switch to placebo after a 12-week fixed-dose stabilization phase. The groups were stratified on the basis of use of mood stabilizers or antidepressants (monotherapy vs adjunctive arms). In both groups, paliperidone monthly significantly reduced relapse compared to placebo, with placebo having a 2.5 times greater risk of relapse overall. As one might expect, the relapse risk was a bit more pronounced in the monotherapy arm compared to the augmentation arm (3.3 times vs 2.0 times). The effectiveness of paliperidone monthly was not particularly surprising, as oral paliperidone has been US Food and Drug Administration (FDA)–approved for treatment of schizoaffective disorder since July 2009. The positive results of this clinical trial led to the approval of paliperidone monthly by the FDA for the treatment of schizoaffective disorder as a monotherapy or an adjunct to mood stabilizers or antidepressants on November 13, 2014. For any medication, FDA approval for additional indications has significant effects. It allows the medication to be marketed by the pharmaceutical company for that use, when prior to the indication this was expressly forbidden. In addition, it can remove potential roadblocks by insurers hesitant to approve a medication for non–FDA-approved indications. In some cases, a new indication dramatically broadens a medication’s use, an example being antipsychotics for antidepressant augmentation. In some cases, formerly generic medications are “repackaged” as proprietary medications for novel usage. Balancing the benefits of expanded use is the possibility that a larger number of patients will be exposed to the risks of these potent compounds. A concern that is not often fully appreciated by clinicians and patients is the potential for the long-term risks of antipsychotics (eg, tardive dyskinesia). Whether these risks are equal, lesser, or even greater in illnesses other than schizophrenia has not been extensively studied.2 The use of paliperidone monthly for schizoaffective disorder is an important development, but it raises the following question: Were patients with schizoaffective disorder not receiving paliperidone monthly before the