Current pharmacological approaches to the treatment of schizophrenia suffer from two major issues; side effects and limited efficacy. The first major unmet medical need is improved side effect liability. Even the best of the modern atypical antipsychotics produce significant side effects with a low therapeutic index. Individuals with schizophrenia have an increased risk of death and, in general a 20% shorter life span84,85 that, in part, may be attributable to the use of current antipsychotic medications. As discussed above, atypical antipsychotics have a clear lower risk of inducing EPS and hyperprolactinemia (with the exception of risperidone) when compared to typical antipsychotics, but the risk still exists. Furthermore, several atypicals, particularly clozapine and olanzapine, increase the risk of sedation, obesity, high blood sugar and diabetes, and dyslipidemia. Very rare cases of neuroleptic malignant syndrome, a rare but potentially fatal reaction characterized by fever, altered mental status, muscular rigidity, and autonomic dysfunction, have also been reported in patients treated with atypical antipsychotic drugs. It is hoped that drugs directed against novel targets will have a much larger therapeutic index with lower associated risk.
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