Plasma levels and clinical improvement--a comparative study of clomipramine and amitriptyline in depression

To see if the clinical efficacy of amitriptyline and clomipramine is related to plasma level of the active drug or its main metabolite, or to the balance between them, plasma levels and clinical progress have been studied in 48 patients taking standard dosage. Dose for dose, plasma levels of clomipramine and desmethylclomipramine are usually higher than those of amitriptyline and its main metabolite nortriptyline, but no significant relationship between plasma levels and clinical improvement was found following clomipramine administration. By contrast, optimum responses to amitriptyline therapy were obtained at plasma levels of 50--100 micrograms/l for amitryiptyline itself and 25--75 micrograms/l for nortriptyline, but when their ratio exceeded 0--7 improvement declined. Steady states were reached after two to three weeks but a crude measure could be obtained from the plasma level after four days' treatment. Clomipramine and amitriptyline appeared to be equally effective, with clomipramine taking slightly longer to relieve depression.