Rational Pharmachotherapy for Affective Disorders : Antidepressants and Their Effects on Biological Markers

The relationship of clinical improvement and the changes of four biological markers was studied in 22 DSM-III diagnosed patients with major depression with melancholia before and during treatment with amitriptyline or mianserin which have different pharmacological and biochemical properties; dexamethasone suppression test (DST) involving ACTH response, blood level of antidepressants, plasma free and total (free+conjugated) MHPG levels, coefficient of variation of R-R interval of ECG (CV R-R). The results were followings; 1. Significant clinical improvement which was rated as reduction of total score of Hamilton Depression Rating Scale was obtained during amitriptyline and mianserin treatment but there was no difference in degree of clinical improvement between two treatment groups. 2. There was no correlation between the blood level of amitriptyline (amitriptyline+nortriptyline) or mianserin and improvement of depressive symptomatology. There was statistically significant and highly positive correlation between amitriptyline dose, mg/kg/day, and serum level at 4th and 8th week. There was highly positive correlation between mianserin dose and 8th week serum level on inpatients. 3. Only 3 of 22 patients were nonsuppressor (13.6%) in 1st 1.0mg DST performed within 7 days after initiation of antidepressant treatment and 21 patients except only one aggravated patient converted suppressor in 2nd DST performed during 4th week of treatment. Cut-off point of DST in this study was 5 μg/dl. The performance of DST in depressive patient may be a useful state dependent marker. The ratio of cortisol and simultaneously measured ACTH in 3 nonsuppressors in 1st DST was higher than that of suppressors and this result suggests peripheral mechanism for DST nonsuppression. 4. CV R-R which reflects autonomic, especially parasympathetic function was significantly reduced during amitriptyline treatment and no significant change during mianserin treatment. There was no significant differrence between the pretreatment value of CV R-R in two patient groups and 12 age-, sex-matched controls. It is suggested that the change in CV R-R may reflect anti-cholinergic effect of given antidepressant. 5. Pretreatment levels of plasma total and free MHPG in patient groups were not different compared with those in 19 age-, sex-matched controls. Free MHPG levels in mianserin treatment group were significantly elevated at 1st week compared with baseline levels. Free MHPG levels in amitriptyline treatment group at 1st week were significantly lower than those in mianserin treatment group. It is suggested that is important for the study of mechanism of antidepressant action and biological markers for affective disorder to introduce the idea of net-transmission in CNS monoaminergic function. The measurement of multiple biological markers may be useful studies of treatment in affective disorders.