Past Issues

Negative symptoms in schizophrenia represent a clinically important target for drug development due to their profound effect on an individual’s ability to function normally. The lack of effective medications for this domain of psychopathology is a major unmet medical need in schizophrenia. Earlier clinical trials for negative symptoms have been criticized mixing primary and secondary negative symptoms as treatment target and lack of standard protocols for clinical trial design. In the first part, The author is reviewing the methodological issues on defining and measuring negative symptoms and on developing the consensus for clinical trial design for negative symptoms. Deficit symptoms and persistent negative symptoms, instead of broadly defined negative symptoms, have been advocated as the treatment target of clinical trial. There were five commonly used interviewbased negative symptom scales with satisfactory psychometric profiles. The consensus has been achieved for the design of clinical trials for negative symptoms. In the second part, the treatment efficacy of different class of drugs on negative symptoms is reviewed. Some second-generation antipsychotics, antidepressants, psychostimulants, glutamate pathway molecules, serotonin receptor antagonists, and anti-inflammatory agents have modest effects on improving negative symptoms than placebo. Although some statistically significant effects on negative symptoms are evident, none has reached the threshold for clinically significant. Several new molecules with potentials in treating negative symptoms are still in development.