Objective To develop a revised equation reflecting the current practice of measuring unbound phenytoin at room temperature, and to evaluate the revised Winter–Tozer method of predicting normalized total phenytoin concentrations in two groups of patients with hypoalbuminemia — elderly nursing home patients and critically ill head trauma patients. Design Albumin, unbound phenytoin, and total phenytoin concentrations were obtained from two sources: prospectively from a group of elderly nursing home patients and by a retrospective chart review of trauma patients enrolled in a previous double-blind, placebo-controlled study. Setting Community nursing homes; a university-affiliated urban teaching hospital. Participants Elderly nursing home patients (n = 46) taking chronic phenytoin therapy and patients enrolled in a double-blind, placebo-controlled study (n = 58) evaluating the use of phenytoin to prevent posttraumatic seizures. Main Outcome Measures Prediction error analysis was performed by using the methods proposed by Sheiner and Beal. Bias and precision were evaluated by calculating the mean prediction error (MPE) and root mean squared error (RMSE), respectively. Results The Winter–Tozer equation consistently overpredicted the normalized phenytoin concentration in the elderly nursing home population (MPE = 3.2, RMSE = 5.9) and the trauma patients (MPE = 3.3, RMSE = 4.8). The equation was revised to reflect the increased protein binding of phenytoin with decreased temperature and resulted in significantly decreased bias in both groups of patients. Conclusions The revised equation is useful in predicting normalized phenytoin concentrations in both elderly nursing home patients and critically ill trauma patients.

Physicians prescribe anticholinergic TCAs principally to treat common non-depressive symptoms in nursing home residents, preferring SSRIs for uncomplicated depression and depression with dementia. They tend to avoid prescribing anticholinergic TCAs other than nortriptyline when they recognize a patient as demented. The data suggest that physicians employ a decision model for antidepressant prescribing that simultaneously recognizes the utility of TCAs in treating non-psychiatric symptoms and the anticholinergic vulnerability of older, especially demented, patients. Whether or not this model leads to optimal patient management requires further study.

Implementation of OBRA-87's nursing home regulations was associated with reductions in use of drugs specifically targeted by this legislation and was a potent stimulus to research, an unanticipated benefit of legislative action. Increased use of anxiolytics, persistent prescribing of anticholinergic antidepressants, enthusiastic adoption of new agents despite a limited research database involving frail patients, and the paucity of new studies reporting data on clinical effectiveness suggest a need for targeted research on treatment outcomes to improve the care of this population.