Studies show a strong relationship between dose and serum concentration (4); however, there is a modest relationship of clinical response or risk of developing long-term side effects to either dose or serum concentration.
A therapeutic window exists for haloperidol; patients who respond at serum concentrations between 5 to 16 ng/mL show no additional improvement at concentrations >16 to 20 ng/mL.(3,5) Some patients may respond at concentrations <5 ng/mL, and others may require concentrations significantly >20 ng/mL before an adequate response is attained.
Because of such inter-individual variation, the serum concentration should only be used as 1 factor in determining the appropriate dose and must be interpreted in conjunction with the clinical status.
Although the metabolite, reduced haloperidol, has minimal pharmacologic activity, evidence has been presented suggesting that an elevated ratio of reduced haloperidol-to-haloperidol (ie, >5) is predictive of a poor clinical response.(3,6) A reduced haloperidol-to-haloperidol ratio <0.5 indicates noncompliance; the metabolite does not accumulate except during steady-state conditions.