Designing outcome studies to determine efficacy and safety of antipsychotics for 'real world' treatment of schizophrenia

Over the last 5 years, some studies have questioned the efficacy of second-generation antipsychotics over first-generation neuroleptics in the treatment of schizophrenia. At the same time, these study results have led to re-examination of their design particularly CATIE and CUtLASS - which essentially measured relatively short-/mid-term outcome and did not always take into account real-world clinical practice and outcome measures (e.g. prevalence of positive acute symptoms, exclusion of comorbidity with substance abuse, predominance of chronic patients, lack of quality of life/wellbeing measures, etc.). In fact, one of the greatest challenges to treatment of schizophrenia is its life-long, multifaceted, functional disability associated with progressive cognitive deterioration after each acute episode. As such, the most important goal of the treatment is not just to deal with acute episodes, but rather to improve long-term outcome. Specifically, we aim for modest improvement and then stabilization of the different clinical dimensions involved in the overall symptomatology (i.e. negative/anergic, impulsive, positive, mood and cognitive impairments), and to achieve 'clinical stabilization' after obtaining a partial or full remission of acute symptoms, thus reducing the risk of a progressive cognitive deterioration. All these aspects need to be properly evaluated in a long-run perspective.