Antipsychotic dose equivalents and dose-years: a standardized method for comparing exposure to different drugs.

BACKGROUND: A standardized quantitative method for comparing dosages of different drugs is a useful tool for designing clinical trials and for examining the effects of long-term medication side effects such as tardive dyskinesia. Such a method requires establishing dose equivalents. An expert consensus group has published charts of equivalent doses for various antipsychotic medications for first- and second-generation medications. These charts were used in this study. METHODS: Regression was used to compare each drug in the experts' charts to chlorpromazine and haloperidol and to create formulas for each relationship. The formulas were solved for chlorpromazine 100 mg and haloperidol 2 mg to derive new chlorpromazine and haloperidol equivalents. The formulas were incorporated into our definition of dose-years such that 100 mg/day of chlorpromazine equivalent or 2 mg/day of haloperidol equivalent taken for 1 year is equal to one dose-year. RESULTS: All comparisons to chlorpromazine and haloperidol were highly linear with R(2) values greater than .9. A power transformation further improved linearity. CONCLUSIONS: By deriving a unique formula that converts doses to chlorpromazine or haloperidol equivalents, we can compare otherwise dissimilar drugs. These equivalents can be multiplied by the time an individual has been on a given dose to derive a cumulative value measured in dose-years in the form of (chlorpromazine equivalent in mg) x (time on dose measured in years). After each dose has been converted to dose-years, the results can be summed to provide a cumulative quantitative measure of lifetime exposure.

Insular cortex abnormalities in schizophrenia: Relationship to symptoms and typical neuroleptic exposure.

BACKGROUND: The insular cortex is a limbic integration region engaged in emotional and cognitive functions. Previously, we found that neuroleptic-naive subjects had abnormally small insular volumes compared with control subjects, with volume directly related to severity of psychotic symptoms. METHODS: To further investigate insular cortex abnormalities and their functional correlates, we measured insular gray matter volume and cortical surface size, using magnetic resonance images among 30 patients with schizophrenia and a matched control group. The sample was designed to represent a variety of phenomenologic profiles to provide sufficient variance in multiple measures, including severity of illness and exposure to neuroleptics (typical only). RESULTS: There were no significant differences in morphology between patients and control subjects; however, among patients, psychotic symptoms were inversely correlated with insular volume, replicating our previous finding in neuroleptic-naive subjects. Neuroleptic exposure had a specific effect on insular morphology: increasing drug exposure (measured in dose-years) correlated with larger insular volume. CONCLUSIONS: This effect of neuroleptic exposure might account for the lack of difference in structural measures in this more chronic sample, whereas the initial study on neuroleptic-naive subjects showed group differences. Further research is needed to investigate the potential relationship between changes in insula volume from neuroleptic exposure and clinical outcome.