CLINICAL HANDBOOK OF SCHIZOPHRENIA

19. Other Medications 193sation in patients with schizophrenia and does not seem to exacerbate positive psychoticsymptoms; however, robust data on the clinical efficacy of bupropion in depression arelacking. A sparse literature supports the use of antidepressant medication in obsessionalstates in schizophrenia, but further studies on the treatment of other anxiety states inschizophrenia are warranted. Finally, clinicians must be careful about drug interactionswhen prescribing antidepressant medications alongside antipsychotics.CO-MEDICATIONS FOR NEGATIVE SYMPTOMSAND COGNITIVE IMPAIRMENTSPatients with schizophrenia who have been stabilized on an antipsychotic commonlyhave persistent negative symptoms (including restricted affect, alogia, apathy, asociality,and anhedonia), as well as cognitive impairments (including impairments in memory, attention,and executive function). These symptom domains are important, because theirseverity is related to the severity of the social and vocational impairments associated withschizophrenia. When the second-generation antipsychotics were first introduced, reportssuggested that these agents were more effective than first-generation agents for both ofthese symptoms domains. More recent data indicate that these advantages may have beenexaggerated by early trial designs, and that when found these advantages are relativelysmall. As a result, both domains are seen as important targets for drug development.Although it would be simpler if broadly effective drugs for treating psychosis were alsoeffective for one or both of these domains, it is also conceivable that the most effectivestrategy may be to supplement an antipsychotic with a co-medication to enhance cognitionor to improve negative symptoms.Translating discoveries from basic neuroscience into new drugs is receiving considerableattention, including a National Institute of Mental Health (NIMH) program whosegoal is to facilitate drug development for cognition enhancement in schizophrenia. Theprogram, titled MATRICS (Measurement and Treatment Research to Improve Cognitionin Schizophrenia; www.matrics.ucla.edu), has already developed methods to measureoutcome in clinical trials, proposed trial designs in collaboration with the U.S. Food andDrug Administration (FDA), and developed a consensus on promising molecular targetsfor drug development. A parallel process has been initiated for negative symptoms.NOVEL MECHANISMSAs illustrated earlier, the second-generation antipsychotics have limitations in treating thewide variety of symptoms that may be present in schizophrenia, including mood symptoms,agitation, and cognitive difficulties. However, as mentioned earlier, a significantnumber of patients’ core symptoms only partially respond to antipsychotic medications.As a result, novel mechanisms are being investigated as both monotherapy and adjunctivetherapy to improve efficacy in treating positive and negative symptoms of this disease, includingsubstance P inhibitors, glutamateric drugs, glycine transporter inhibitors, andother agents.Although most of these new agents are still in the preliminary phases of discovery,one mechanism that has received quite a bit of clinical and scientific interest of late is thatof the omega-3 polyunsaturated fatty acids. The hypothesis for the efficacy of fatty acidsis based on the premise that phospholipids are a significant component of neuronal membranes,and that abnormalities of phospholipid metabolism may be present in patientswith schizophrenia. This has given rise to the theory that omega-3 polyunsaturated fatty