Asenapine in the treatment of negative symptoms of schizophrenia: clinical trial design and rationale.

Although the positive symptoms of schizophrenia are more likely than the negative symptoms to result in a patient's hospitalization, positive symptoms tend to respond more completely to antipsychotic drugs.When positive symptoms are controlled, residual negative symptoms may remain. If these negative symptoms persist, they can have a considerable impact on a patient's ability to function in society. Current therapies have only a limited effect on negative symptoms. Consequently, broad-spectrum agents that effectively treat both positive and negative symptoms are needed. One obstacle to the regulatory approval of an agent for treating negative symptoms is the difficulty of designing a trial to demonstrate efficacy for these symptoms. Agreeing on a definition of negative symptoms, establishing patient inclusion criteria, and determining how to account for confounding factors represent only a few of the challenges to study design. How these challenges can be met is illustrated in the design of a series of clinical trials to assess the efficacy of asenapine, a psychopharmacologic agent being developed for the treatment of schizophrenia and, in particular, the treatment of negative symptoms associated with schizophrenia. These trials, the protocols for which are described in this paper, will not only determine the efficacy of asenapine but will add to our knowledge of patients with predominant, persistent negative symptoms, an understudied and inadequately treated patient population.