Concentration-response relationship in imipramine treatment of diabetic neuropathy symptoms

A single-blind imipramine dose titration study was conducted in 15 diabetic patients with neuropathy symptoms. The effect of treatment was evaluated by use of visual analog scales. Imipramine doses were individually adjusted until doses yielded plasma concentrations of imipramine plus desipramine that were well above 400 nmol/L or until all neuropathy symptoms had vanished. In all except one patient, there was marked relief of symptoms. In the responding patients (n = 14), much of the effect occurred at plasma levels of imipramine plus desipramine below 100 nmol/L, but a considerable interindividual variation was observed. Concentrations above 400 to 500 nmol/L were required to ensure maximal effect in all patients, and we did not find any indication of a decreased effect at high drug levels. The dose-dependent kinetics of imipramine was confirmed, and dose increments should therefore be carried out in small steps and preferably with monitoring of drug levels.