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CNS Spectr. 2008 May;13(5 Suppl 9):1-16.

Dosing atypical antipsychotics.

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Department of Psychiatry, University of Florida, Gainesville, FL, USA.


Atypical antipsychotic treatment strategies have tended to change significantly from the time new drugs are introduced to the market. Because these drugs are associated with so many side effects, dosing strategies are largely based on the avoidance of adverse effects. A great number of issues complicate the task of effectively dosing atypical antipsychotics, including great variability and unpredictability in individual response. This often leads to extensive periods of trial and error as well as patient suffering, while physicians search for an optimum treatment. The mechanisms of action of these drugs are not entirely understood; they can be effective for both psychosis and mood disorders, possibly via actions on different systems or circuits. Furthermore, a resolution to the dilemma of dosing once or twice daily depends on issues of patient compliance and drug efficacy. This supplement puts these issues into perspective by illustrating historical discrepancies in antipsychotic use between clinical trials and practice, discussing individual response variability to antipsychotic treatment, describing current theories of antipsychotic mechanisms of action, and speculating as to the future of antipsychotic treatment strategies. The following unmet needs regarding dosing atypical antipsychotics were revealed following a vigorous assessment of activity feedback, expert faculty assessment, literature review, and through new medical knowledge: (1) although many clinicians generalize that higher doses are associated with greater efficacy and more side effects, the efficacy and tolerability profile for different doses of atypical antipsychotics are far less straightforward than that; (2) physicians continue to face huge issues of patient adherence when treating schizophrenia and bipolar disorder, which may be mitigated by addressing the most troublesome side effects caused by antipsychotics; (3) research on genetics, neurocircuitry, and new treatment methods in schizophrenia is ongoing; clinicians need to be educated on new treatment strategies as data accumulate so that they are prepared to implement these tools once they become available.

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