The goal of
antipsychotic drug development efforts over the past 10 years has been to develop agents with increased efficacy and safety and fewer of the side effects commonly associated with the older
antipsychotic medications. The newer agents, often called atypical
antipsychotics, are effective in treating both the positive and negative symptoms of
schizophrenia and are associated with fewer neurological- and endocrine-related side effects compared to the older agents. As a result, patients are likely to remain on
therapy longer, preventing relapses and costly hospitalizations.
Quetiapine fumarate (
Seroquel) is the most recently introduced atypical
antipsychotic and is indicated for the management of the manifestations of
psychotic disorders and
schizophrenia.
Quetiapine, like
clozapine (the archetypal atypical
antipsychotic), interacts with a broad range of
neurotransmitter receptors and has a higher affinity for
serotonin (5-HT(2A)) receptors relative to
dopamine (D(2)) receptors in the brain. Further,
quetiapine's pharmacological effects appear selective for the mesolimbic and mesocortical
dopamine systems, which are believed to be the areas of the brain responsible for the
therapeutic effects of
antipsychotics. In contrast to most standard
antipsychotics and some atypical
antipsychotics,
quetiapine's effects on the nigrostriatal
dopamine system, which is responsible for the extrapyramidal (or motor) side effects, are minimal.
Quetiapine also has minimal activity on
dopamine receptors in the tuberoinfundibular
dopamine system, thereby avoiding the problem of
hyperprolactinemia, common with the standard
antipsychotics and some atypical
antipsychotics. Because of these properties,
quetiapine is an effective
antipsychotic agent with a relatively benign side effect profile. Several large, placebo- and active-controlled, multicenter trials have shown
quetiapine to be effective against both positive (e.g.,
hallucinations, delusions) and negative symptoms (e.g., emotional withdrawal, apathy) and to have benefits in reducing hostility, aggression and affective symptoms. Patients on long-term treatment report high compliance, good satisfaction, increased ability to function and improvements consistent with a better quality of life. Because of
quetiapine's excellent tolerability profile, its use is particularly appropriate in patients especially sensitive to adverse effects, e.g., elderly patients with psychotic symptoms and other
neurological disorders such as Parkinson's and
Alzheimer's disease.