No Change of Amitriptyline Concentration by Comedication of Tranylcypromine

In 5031 blood samples of 1390 stationary patients of our clinic under treatment with amitriptyline the concentration of amitriptyline and nortriptyline was measured by hplc. By inspection of the medical file the comedication was verified. A multiplicity of additional drugs was given: most frequently haloperidol (28%), lorazepam (21%), lithium (11%), chloraldurate (10%), chlorazepate (6%), biperiden (5%), dihydroergotamine (5%), digoxine (5%) and tranylcypromine (4.4%).

Related to the number of patients, 6.5% had a comedication with tranylcypromine. Therefore, tranylcypromine is one of the more often used comedications. The mean number of medicaments additional to amitriptyline is 1.54. In the tranylcypromine group the mean number is 2.4. This is nearly one drug more (tranylcypromine). This group has no significant difference in age, gender or dose of amitriptyline. It can be concluded, that in this group the dose of amitriptyline or the number of additional drugs was not reduced.

No significant change of the amitriptyline concentration influenced by tranylcypromine could be detected. That is in accordance with Salsali et al. (2004), who found in in vitro studies an enzymatic inhibitory effect (mainly CYP2C19), but only with higher doses than therapeutically used. The same (nonsignificant) result was shown with the ratio amitriptyline and dose. Pharmacokinetically no influence is seen with tranylcypromine on amitriptyline metabolism.

The described therapeutic increase (White and Simpson, 1981, Schmauss et al., 1988) by concomitant medication of amitriptyline and tranylcypromine can therefore only be explained by pharmacodynamic, not by pharmacokinetic effects.

References: Salsali M, Holt A, Baker GB; Cell Mol Neurobiol 24, 63–76 (2004). Schmauss M, Kapfhammer HP, Meyr P, Hoff P; Prog Neuropsychopharm Biol Psychiatry 12, 523–532 (1988). White K, Simpson G; J Clin Psychopharmacol 1, 264–282 (1981).