Future Trends

The advent of the second-generation atypical antipsychotics has revolutionized pharmacological treatment of schizophrenia and other psychotic disorders. In contrast to the first-generation conventional neuroleptics, these second-generation antipsychotic agents possess a broader spectrum of efficacy and cause fewer motor side effects, such as extrapyramidal symptoms (EPS) and tardive dyskinesia. Despite their substantial advantages, however, these second-generation agents also have significant limitations both in terms of efficacy and adverse effects. Adverse effects contribute to the major problem of medication noncompliance in schizophrenia; whereas injectable formulations of antipsychotics help with regard to this problem, no atypical agent is currently available in an injectable form (acute or depot). While possessing a broader spectrum of efficacy than conventional agents, even atypical antipsychotics are generally unable to completely normalize cognitive function or eliminate negative and mood symptoms. In fact, significant cognitive deficits and negative symptoms remain in schizophrenic patients treated with atypical agents. Although clozapine (and other novel agents to a less substantiated extent) may be effective in patients partially or completely refractory to treatment with conventional antipsychotics, these agents do not work in a significant proportion of patients. There is significant variation in the way patients respond to different antipsychotic medications, and currently there is no way of predicting which antipsychotic will work best for a particular patient and at what dose.

Finally, although our current pharmacological armamentarium has obvious limitations, it is also clear that "usual treatment" generally falls far short of the "best possible." Despite the publication of several treatment guidelines, there is significant variation in pharmacological treatment practice that cannot be explained away by "patient heterogeneity"; attempts to promote evidence-based "best possible" phar-macotherapy of schizophrenia have hitherto been unsuccessful. Efforts to address each of the above shortcomings are currently underway. While it is difficult to predict precisely when each of the following tools will become available to the clinician, some of these strategies are at very advanced stages of study, whereas others are at a very preliminary stage.

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