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SEROTONIN DOPAMIN ANTAGONISM – THE SDA HYPOTHESIS IN THE MANAGEMENT OF SCHIZOPHRENIA |
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Tim Lambert |
| Traditional
treatment of schizophrenia with standard neuroleptics such as haloperidol
has lead to some improvements in the control of positive symptoms of schizophrenia.
Unfortunately, traditional agents are invariably accompanied by side effects
such as extrapyramidal symptoms (EPS) and neuroleptic-induced deficit cognitive
symptoms (NIDS). In addition these agents may worsen negative symptoms.
The atypical agents such as Risperidone have been shown to improve positive,
negative and neurocognitive symptom domains and substantially reduce EPS.
A number of hypotheses have been generated to account for the action of
the "atypical" agents. Risperidone, amongst others, can be modeled
on the basis of high ratio of serotonergic 5HT2A antagonism
as opposed to lower D2 antagonism. This is called the SDA hypothesis
of atypical neuroleptics.
This paper briefly reviews serotonin and dopamine function in the brain and presents a heuristic model to account for atypicality using the SDA percepts. The application of the model to understanding how low doses of atypicals may be crucial to long term outcome is discussed. |