Relationship of free nortriptyline levels to therapeutic response

The relationship between the free plasma concentration of nortriptyline and therapeutic response was examined. Eighteen depressed inpatients were treated for 21 days with steady state total nortriptyline plasma concentrations between 50-150 ng/ml. Steady state free nortriptyline concentrations were measured. The therapeutic nortriptyline response was measured by administering the Hamilton and the Carroll Rating scales at day zero and day 21. Statistical relationships between free levels of drug and clinical response were found to be insignificant. Qualitative assessment of the data suggest that free serum levels of nortriptyline in excess of 10 ng/ml may have an inhibitory effect on clinical response.