Novel antipsychotics and negative symptoms.

Negative symptoms are a key feature of schizophrenia. Novel (atypical) antipsychotic drugs, unlike conventional antipsychotics, cause substantial reductions in Positive and Negative Symptom Scale (PANSS) scores. Negative symptoms, however, can arise from both the pathology of the disease (primary negative symptoms) and as side effects of antipsychotic drugs (secondary negative symptoms). Before the efficacy of a drug against negative symptoms can be determined, the physician must establish whether the positive results stem from reductions in primary negative symptoms or are merely due to improved extrapyramidal tolerability. Until recently, shortcomings in the design of clinical trials and the lack of distinction between primary and secondary symptoms made it impossible to answer this question. However, advances in clinical trial methodologies now make it possible to assess negative symptoms accurately, and a complex statistical approach, the path analysis, has been developed to differentiate between the direct and indirect effects of antipsychotic drugs on negative symptoms. With this approach, it has been shown that the efficacy of novel antipsychotics, such as sertindole, against negative symptoms is achieved largely through direct effects on primary negative symptoms. The requirements for an accurate assessment and differentiation of negative symptoms are outlined, and the importance of this for improving the treatment of schizophrenia is emphasized.