EMERGING ROLES FOR NOVEL ANTIPSYCHOTIC MEDICATIONS IN THE TREATMENT OF SCHIZOPHRENIA
Section snippets
THE NEED FOR ADVANCES IN ANTIPSYCHOTIC DRUG THERAPY
The introduction of chlorpromazine into clinical practice more than 40 years ago revolutionized the management of schizophrenia, and provided the first sound scientific basis for the study of its cause and treatment. Chlorpromazine and the other early drugs used to treat psychoses produced what Delay and Deniker54 termed the neuroleptic syndrome. This term was intended to contrast the effects of the antipsychotic drugs with those of such classic CNS depressants as general anesthetics,
Early Ideas About Atypical APDs
At first glance, it seems unusual that a similar pattern of both therapeutic action and side effects held for antipsychotic drugs that were members of structurally distinct chemical classes (i.e., phenothiazines, butryophrenones, thioxanthenes, substituted benzamides, dibenzoxepines, and indolones). Yet the methods (first psychopharmacologic and later biochemical) that were employed in drug discovery were based on selection of compounds that were chlorpromazine-like, and could do little else
Neuroleptic Treatment-Resistant Patients
It is now recognized that up to 40% of all schizophrenic patients fail to respond therapeutically to traditional APDs and show persistent psychotic symptoms,90 and as many as 60% may have substantial residual symptoms of one form or another.137 At one time, this phenomenon was thought to occur in only a minority of schizophrenic patients;39 however, it is now recognized as a major problem in the management of schizophrenia. The inability to respond to treatment appears to develop for several
Mechanisms by Which a Drug May be Atypical
The data discussed earlier suggests several strategies by which atypical APDs may be developed. This information can be used to provide a framework for much of the discussion that follows. It is helpful to consider the following as specific strategies, although within each one, variations are possible.
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Magic bullet drugs with significant selectivity for a dopamine receptor isoform
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Magic bullet drugs with significant selectivity for a nondopamine receptor (i.e., a glutamate receptor)
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Magic
CONCLUSION
The availability of clozapine has heralded a new era in the treatment of schizophrenia. Antipsychotic treatment can be pursued without the intrusion of obligatory acute and chronic EPSE, and clinical efficacy beyond that obtainable with typical APDs is a realistic clinical goal. Furthermore, renewed interest in the development of other atypical or novel APDs has occurred, and this will no doubt soon change the manner in which schizophrenia and other psychoses are managed.
There is increasing
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Metabotropic glutamate receptor 5 in the pathology and treatment of schizophrenia
2013, Neuroscience and Biobehavioral ReviewsCitation Excerpt :An imbalance in dopaminergic neurotransmission has been well documented in schizophrenia (Toda and Abi-Dargham, 2007). Accumulated evidence includes the ability of dopamine-reuptake inhibitors to induce hallucinations and delusions homologous to the positive symptoms of schizophrenia (Matthysse, 1974), in addition to the capability of dopamine D2 receptor antagonists to successfully ameliorate some psychotic symptoms such as hallucinations and delusions (Andersson et al., 1998). However, dysfunction of the dopaminergic system does not account for the more discreet and debilitating symptoms seen in the disease, which have been attributed to disruptions in glutamatergic circuitry (Tsai and Coyle, 2002).
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Address reprint requests to Jeffrey A. Lieberman, MD, Department of Psychiatry, University of North Carolina School of Medicine, 7025 Neurosciences Hospital, Chapel Hill, NC 27599–7160
This was supported by a National Institute for Mental Health (NIMH) Research Scientist Development Award (MH–00537) to Dr Lieberman and a NIMH Mental Health Clinical Research Center (MH–33127).