Maximizing Antipsychotics' Effectiveness in Schizophrenia Through Moderation

Derick E. Vergne, MD


July 06, 2015

In This Article

Increasingly Complex Pathways

Psychosis is defined as a mental state characterized by a disconnection from reality. Its etiology can be traced to multiple origins—from medical causes, such as thyrotoxicosis; to neurologic ones, such as seizure disorders; to purely psychiatric causes, such as schizophrenia. Disconnection from reality can occur in the form of abnormalities in the way in which the world is perceived (hallucinations) and the reaction to such perceptions (abnormal beliefs, such as delusions or paranoia).

Antipsychotics are the agents of choice to alleviate most psychotic disorders. They were originally thought to exert their action by blocking the dopamine-2 (D2) receptors in the striatum of the basal ganglia (located at the base of the forebrain, the most anterior developmental structure of the brain). Current research supports the notion that the neurochemistry of schizophrenia is more complicated, instead involving additional neurotransmitter systems, such as glutamate, serotonin, and other neuropeptides (eg, neurotensin, cholecystokinin, and corticotropin-releasing factor).[1]

Although the current state of knowledge in schizophrenia and psychoses has become increasingly complex, the dopamine system continues to play a key role, given that it is the main system manipulated with antipsychotics. Despite the current categorization of antipsychotics into "typical" and "atypical," each medication has different characteristics that are based on other neurotransmitter systems they might modulate in addition to the dopamine system.

For instance, we know by way of clinical experience that even though haloperidol and chlorpromazine are both considered typical antipsychotics, the latter causes more pronounced sedation, weight gain, constipation, and blurred vision. This is due to chlorpromazine's effects on histamine and acetylcholine, which are not shared by haloperidol. In fact, the histaminergic and cholinergic effects of many of the current typical and atypical antipsychotics are often underappreciated and may interfere with the very clinical effects with which our patients are dealing.[2]


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