This led to the emergence of the dysregulation hypothesis, which suggests that dopaminergic pathways are not in homeostatic balance, leading to hyperactivity in certain regions of the brain and hypoac-tivity in others. In general, serotonin activity has an inhibitory effect on dopaminergic pathways. The dysregula-tion theory has been broadened by postulating a D2/5-hydroxytriptamine (5-HT2) imbalance, with positive symptoms resulting from an increase in the D2/5-HT2 activity ratio in the mesolimbic region of the brain and negative symptoms from a decrease in the ratio in the frontal cortex . Other neurochemicals such as glutamate and acetylcholine are being studied with respect to their role in the etiology of schizophrenia . Research is now focusing on alternate mechanisms of action than those of the conventional agents, attempting to develop antipsychotics without EPS while improving response rates and ameliorating negative symptoms and cognitive deficits. These research endeavors have given rise to a new category of agents commonly referred to as the atypical, second generation or novel antipsychotics, or serotonin-dopamine antagonists(Table 1). levitra super active plus
Table1 Half-life and dosage comparison of second generation antipsychotics
|Drug||Half-life (h)||Dosage interval||Average dosage range (mg/day)|
|Clozapine||6-30||BID-TID||300-450 (maximum 900 mg/day)|
Not yet available in North America. bid Twice daily; uu tach day; iiu ihree imes daily. Data from references 21,34,47,56,58,77
This narrative review is based on clinically relevant evidence specific to the issues related to the use of the second generation antipsychotics in schizophrenia. We await the completion and dissemination of systematically derived clinical practice guidelines, such as those developed by the Royal College of Psychiatrists Research Unit (British Psychological Society) to further our interpretation of the current evidence.
The pharmacology, efficacy, tolerability and pharmacoeco-nomic impact are discussed for each agent. As well, clinically important drug-specific issues are also presented.