Comparison of safety between individualized and empiric dose regimen of amitriptyline in the treatment of major depressive episode.

To accomplish therapeutic goal it is necessary to adjust the dose of medication to be right for every single patient. This procedure of dose adjustment is individualized dose regimen. First of all, pharmacokinetic aspects should be revised, including parameters such as resorption, distribution, metabolism and secretion of drug. For these purposes, the authors developed and clinically assessed the modified Bayesian method supported by original basic computer program. The aim of research was to compare frequency of adverse events in cases of individualized and empiric dose regimens of amitriptyline in the treatment of major depressive episode. Sixty subjects (32- 65 years old), with major depressive disorder (International Classification of Disease, 10th revision), were randomly assigned and single- blinded to take individualized (experimental group, n=30) or empiric (control group, n=30) doses of amitriptyline for 8 weeks. CGI scale and originally designed questionnaire were used for adverse events assessment. In experimental group, 69 complaints on nine different types of adverse effects were recorded during eight-week treatment period. Severe adverse events, such as confusion or arrhythmia, were not registered in this subgroup. In control group, 111 complaints on twelve different types of adverse effects were recorded. Most common were anticholinergic effects, but during the third and fourth week from baseline, some severe adverse events were observed: tremor (16%), fatigue (16%), in one of the subjects confusion occurred and arrhythmia in another. Analyzing of the results according to CGI scale for adverse events showed that, during the treatment period, adverse events were less frequent in experimental group. This was particularly obvious in the first four weeks of treatment, when statistically significant difference (p<0.05) was observed.