CLINICAL HANDBOOK OF SCHIZOPHRENIA

560 VIII. SPECIAL TOPICStion, restricted expression of emotion, and reduced social drive). These symptom domainsare relatively independent of each other, have different patterns of onset, and different treatmentresponses. Negative symptoms appear as trait pathology and do not vary with the severityof psychosis. The impact of some aspects of negative symptoms on outcome appearsstronger than that of psychosis. In addition, impaired cognition is almost universal in personswith schizophrenia. This impairment, measured with neuropsychological tests, haslow to nil correlation with the symptom domains. Impaired cognition, however, is a primarydeterminant of poor functional outcome. The implication of this body of data is that schizophreniacan be deconstructed into separable domains of pathology, and that concepts of remissionand recovery must be considered for each domain.Schizophrenia can be fairly viewed as a disorder involving psychosis, but an almostexclusive emphasis on psychosis in diagnosis and treatment has distorted the concept ofschizophrenia. The presence of psychosis has been foremost in assessing response in clinicaltrials and real-world practice. But concepts of remission and recovery based on psychosisruns afoul of observations of continuing negative symptoms, impaired cognition,and poor functioning. Despite the low relationship between a psychotic symptom courseand other aspects of pathology and function, the presumption that treating psychosis iskey to improved outcomes has persisted. Treatment research, especially clinical trials ofpharmacotherapy, has reported outcomes in percentage of improvement in symptomscores, or percentage of patients crossing an improvement threshold. These approacheshave no known relationship to remission or recovery, and the field has been criticized forbeing content with improvement without aggressively pursuing remission.The impact of overemphasizing psychosis can be illustrated by the influence ofantipsychotic drug trials on the concept of remission. During the 1950s and 1960s, effectsof drug–placebo differences on measures of time in the hospital, level of psychoticsymptoms, and relapse rates were very robust. The differences were direct, and it waseasy to understand the implications for treatment. However, other outcome measureswere virtually ignored, and it is still unclear how much improvement in long-term outcomeshas been achieved (Hegarty, Baldessarini, Tohen, Waternaux, & Oepen, 1995).More recent clinical trials show less robust drug–placebo differences, presumably becausemore treatment-resistant individuals are participating in clinical trials. The introductionof clozapine, and the documentation of superior efficacy in treatment-resistant individuals,stimulated hope for more favorable outcomes. This hope, carried forward with second-generationantipsychotic drugs, has not been fulfilled. Cochrane Library reviewshave failed to find superior efficacy for second-generation antipsychotic drugs other thanclozapine, results substantiated in the recent publicly funded Clinical Antipsychotic Trialsof Intervention Effectiveness (CATIE; Lieberman et al., 2005) in the United States andCost Utility of the Latest Antipsychotic Drugs in Schizophrenia (CUtLASS; Jones et al.,2006) trial in the United Kingdom, and in industry-sponsored first-episode studies inwhich lower doses of first-generation drugs were used. Rather than evaluating treatmentswith concepts of remission, studies have usually reported percentage of improvement andnumber of subjects achieving a 20% reduction in a symptom rating scale. It is difficult totell from such measures whether a clinically meaningful difference is achieved. In fact, itwould appear that such changes reflect a very small improvement—which may be barelynoticeable clinically (Leucht et al., 2003).A BACKGROUND ON REMISSION VERSUS RECOVERYThe medical concept of remission implies significantly reducing core features of a disease,achieving a certain functional level, and remaining stable. The medical concept of recov-