Dosing of antipsychotics in schizophrenia across the life-spectrum

Age effects on dosing of antipsychotics in schizophrenia and mechanisms underlying those effects have not been well understood. The objective of this article is to review the literature regarding effects of age on antipsychotic dosing in schizophrenia and potential mechanisms underlying the age-related antipsychotic sensitivity. According to prescription surveys, age appears to have biphasic effects on prescribed antipsychotic dose. The dose increased with age through the third decade, subsequently plateaued, and decreased after the fifth decade. The first half of this inverted U-shaped relationship may be attributable to a deterioration process in the early phase of schizophrenia and the contribution of ‘tachyphylaxis’ of antipsychotics on the dopaminergic system. The following age-related decline in prescribed dose is likely associated with physiological aging. Recent data suggest that this increased antipsychotic sensitivity with age comes from age-related functional decline in the dopaminergic system, including endogenous dopamine level and dopamine receptor density. Although the evidence on potential mechanisms underlying age effects on antipsychotic dosing is still limited, alterations in the dopaminergic system due to aging and chronic exposure to this drug may contribute to the inverted U-shaped relationship between dose and age. This age-related antipsychotic sensitivity highlights the importance of finding the lowest possible effective dose of antipsychotic drugs as patients age to enhance therapeutic effects as well as minimize their side effects.