Purpose: Research supporting the "early-onset" theory of antipsychotic activity is reviewed, with an emphasis on psychometric assessment of early response to antipsychotic agents as a tool for optimizing schizophrenia treatment outcomes.
Summary: A growing body of evidence indicates that a poor response to antipsychotic therapy in the first weeks of schizophrenia treatment may justify a prompt switch to alternative medication in some cases. In placebo-controlled trials of both first- and second-generation antipsychotics, nonresponse at week 1 or 2, as determined with assessment instruments such as the Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Syndrome Scale (PANSS), was found highly predictive of nonresponse at week 4 or later; however, an early favorable response to a particular antipsychotic agent does not appear to be a similarly strong predictor of continued responsiveness. While the available evidence indicates that the BPRS, PANSS, and other scoring tools can be useful in guiding schizophrenia treatment decisions, it also emphasizes the importance of patient-specific factors (e.g., severity of illness at diagnosis, age at symptom onset, premorbid adolescent functioning) as determinants of both initial and longer-term antipsychotic response.
Conclusion: The current evidence suggests that early nonresponse to antipsychotic treatment may predict subsequent non-response, though early response is not necessarily indicative of future response. If patients do not respond to treatment within the first two weeks of an acute exacerbation, clinicians (being cognizant of patient-specific factors) should consider switching antipsychotic agents, except in patients with first-episode psychosis, for whom a longer trial of the initially prescribed therapy appears to be appropriate.