Medications for first-episode psychosis: making a good start.

Abstract

Early treatment for individuals experiencing schizophrenia has received increasing attention because of its potential to alter the course of illness and improve outcomes (1). A critical component of optimal early treatment includes appropriate use of medications. Because of differential responses to medications in first-episode and multiepisode schizophrenia, prominent guidelines suggest different treatment practices for these patient groups (2, 3). For example, the 2010 Schizophrenia Patient Outcomes Research Team (PORT) underlines the importance of using low dosages of medication and specifies thatolanzapineandclozapineshouldnotbefirst-linetreatments because of their risks of adverse effects (3). Becausemedication experiences for individuals at the beginning of treatment may have a lasting impact on their attitudes toward medication and courseof illness, this is acritical timetooptimizeprescribing.To theextent thatadhering to theguidelines leads tobetterefficacy, tolerability, and positive interactions with mental health professionals, this could have a significant impact in first-episode patients. TheRecoveryAfteranInitialSchizophreniaEpisodeproject’s Early Treatment Program (RAISE-ETP) study is a nationwide comparative effectiveness trial that enrolled404 individualswith a schizophrenia spectrum diagnosis at 34 community sites throughout thecountry. Studyparticipantshadreceived less than 6monthsof antipsychotic treatmentat enrollment.Therelatively large sample and geographic breadth of the study provided the first opportunity to characterize typical community treatment of early-phase schizophrenia patients in the United States. In this issue, Robinson et al. (4) report on prescription practices observed in first-episode schizophrenia in the RAISE-ETP study. The investigators obtained detailed information regarding each participant’s prescribed medications at study entry and determined whether the medication treatment was consistent with practice guidelines. The investigators also examined participantand system-level factors associated with medication patterns that did not conform to practice guidelines and therefore could “benefit from changes.” Theinvestigators foundevidenceofpotentiallyproblematic prescribing for 159 individuals (39.4%of thesample).Themost common issues were use of an antidepressant along with an antipsychotic without a clear indication; prescription of olanzapine; and use of more than one antipsychotic. A small subgroup also had psychotropic medications prescribed without antipsychotics. While the article focuses on potential prescribing problems, it isfirstworthnoting that theprescribing formore than 60% of the sample appeared to follow existing guidelines. Given that guidelines are notmeant to dictate prescribing for an individual patient, the appropriate benchmark for conformant practice is not clear. In a study of quality of schizophrenia care, Young et al. (5) found that for 34 of 84 patients receiving poor-quality care, patient factors such as poor adherence and substanceusecontributedto theproblematicprescribing.Some nonconformant prescribing may in fact be appropriate for particular patients given their history of treatment response, their symptoms, and their preferences. It isalso important to note that prescribing that conforms to guidelines is not necessarily optimal. Guideline-conformant treatment suggests but is not synonymous with highquality care. Notwithstanding the limitations of prescribing guidelines, this studyunderlinesseveral concerns inprescribing psychotropic medications in individuals experiencing a first episode of psychosis. With respect to antipsychotic prescribing, use of combinations of antipsychotics is not supported by evidence and may be associated with more adverse effects (3, 6). This is particularly important in the careof individualswith first-episode psychosis, who are extraordinarily vulnerable to medication side effects (3). The increased complexity of dosage schedules involving polypharmacy, the increased likelihood of adverse effects, and the lack of evidence for effectiveness all argue strongly against polypharmacy in this population. If two individual antipsychotics do not provide adequate benefit, evidence strongly supports and guidelines recommend using clozapine rather than combinations of antipsychotics (2, 3). Clinicians who rarely treat first-episode patients may not be awareof the extent of problemswith olanzapine use in this population.ThePORTrecommends against usingolanzapine